leukocyte elastase

Summary

Summary: An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC 3.4.21.37.

Top Publications

  1. pmc Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps
    Venizelos Papayannopoulos
    Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
    J Cell Biol 191:677-91. 2010
  2. ncbi Neutrophil extracellular traps kill bacteria
    Volker Brinkmann
    Microscopy Core Facility, Max Planck Institute for Infection Biology, Schumannstrasse 21 22, 10117 Berlin, Germany
    Science 303:1532-5. 2004
  3. pmc Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth
    A McGarry Houghton
    Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Nat Med 16:219-23. 2010
  4. ncbi The paradox of tumor-associated neutrophils: fueling tumor growth with cytotoxic substances
    A McGarry Houghton
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Cell Cycle 9:1732-7. 2010
  5. ncbi LL-37 complexation with glycosaminoglycans in cystic fibrosis lungs inhibits antimicrobial activity, which can be restored by hypertonic saline
    Gudmundur Bergsson
    Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland
    J Immunol 183:543-51. 2009
  6. pmc Breast cancer cell uptake of the inflammatory mediator neutrophil elastase triggers an anticancer adaptive immune response
    Elizabeth A Mittendorf
    Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 72:3153-62. 2012
  7. ncbi Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis
    A Belaaouaj
    Respiratory and Critical Care, Department of Medicine, Cell Biology, Washington University School of Medicine at Barnes Jewish Hospital, St Louis, MO 63110, USA
    Nat Med 4:615-8. 1998
  8. ncbi Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1
    Hironori Waki
    Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo, Tokyo 113 8655, Japan
    Endocrinology 146:790-6. 2005
  9. ncbi Potent inhibitors of beta-tryptase and human leukocyte elastase based on the MCoTI-II scaffold
    Panumart Thongyoo
    Department of Chemistry and Chemical Biology Centre, Imperial College London SW7 2AZ, UK
    J Med Chem 52:6197-200. 2009
  10. ncbi Neutrophil-derived elastase induces TGF-beta1 secretion in human airway smooth muscle via NF-kappaB pathway
    Kang Yun Lee
    Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 199 Tun Hwa N Rd, Taipei, Taiwan
    Am J Respir Cell Mol Biol 35:407-14. 2006

Detail Information

Publications269 found, 100 shown here

  1. pmc Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps
    Venizelos Papayannopoulos
    Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
    J Cell Biol 191:677-91. 2010
    ....
  2. ncbi Neutrophil extracellular traps kill bacteria
    Volker Brinkmann
    Microscopy Core Facility, Max Planck Institute for Infection Biology, Schumannstrasse 21 22, 10117 Berlin, Germany
    Science 303:1532-5. 2004
    ..NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria...
  3. pmc Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth
    A McGarry Houghton
    Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Nat Med 16:219-23. 2010
    ..Additionally, to our knowledge, this is the first description of a secreted proteinase gaining access to the inside of a cell and altering intracellular signaling...
  4. ncbi The paradox of tumor-associated neutrophils: fueling tumor growth with cytotoxic substances
    A McGarry Houghton
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Cell Cycle 9:1732-7. 2010
    ..Alternatively, strategies designed to generate highly activated and cytotoxic neutrophils within the tumor microenvironment may provide a means to unleash the tumoricidal potential of the host's innate immune response...
  5. ncbi LL-37 complexation with glycosaminoglycans in cystic fibrosis lungs inhibits antimicrobial activity, which can be restored by hypertonic saline
    Gudmundur Bergsson
    Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland
    J Immunol 183:543-51. 2009
    ....
  6. pmc Breast cancer cell uptake of the inflammatory mediator neutrophil elastase triggers an anticancer adaptive immune response
    Elizabeth A Mittendorf
    Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 72:3153-62. 2012
    ..Taken together, our findings reveal a previously unknown mechanism of antitumor adaptive immunity that links cancer cell uptake of an inflammatory mediator to an effective cytolytic response against an important breast cancer antigen...
  7. ncbi Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis
    A Belaaouaj
    Respiratory and Critical Care, Department of Medicine, Cell Biology, Washington University School of Medicine at Barnes Jewish Hospital, St Louis, MO 63110, USA
    Nat Med 4:615-8. 1998
    ..Our data indicate that neutrophils migrate normally to sites of infection in the absence of NE, but that NE is required for maximal intracellular killing of Gram negative bacteria by neutrophils...
  8. ncbi Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1
    Hironori Waki
    Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo, Tokyo 113 8655, Japan
    Endocrinology 146:790-6. 2005
    ..The cleavage was thought to be mediated by leukocyte elastase (also known as neutrophil elastase) based on the following observations...
  9. ncbi Potent inhibitors of beta-tryptase and human leukocyte elastase based on the MCoTI-II scaffold
    Panumart Thongyoo
    Department of Chemistry and Chemical Biology Centre, Imperial College London SW7 2AZ, UK
    J Med Chem 52:6197-200. 2009
    ..possess potent activity against two therapeutically significant serine proteases: beta-tryptase and human leukocyte elastase. These results suggest that MCoTI-II is a versatile scaffold for the development of protease inhibitors ..
  10. ncbi Neutrophil-derived elastase induces TGF-beta1 secretion in human airway smooth muscle via NF-kappaB pathway
    Kang Yun Lee
    Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 199 Tun Hwa N Rd, Taipei, Taiwan
    Am J Respir Cell Mol Biol 35:407-14. 2006
    ..These data suggest that NE upregulates TGF-beta1 gene expression and release via My88/IRAK/NF-kappaB pathway, possibly through activation of TLR4, and shed light on a potential role of neutrophils in the pathogenesis of asthma...
  11. ncbi Primary human alveolar type II epithelial cell chemokine release: effects of cigarette smoke and neutrophil elastase
    Ian R Witherden
    Lung Cell Biology, National Heart and Lung Institute, Imperial College of Science, London, United Kingdom
    Am J Respir Cell Mol Biol 30:500-9. 2004
    ..We hypothesize that reduced ATII cell-derived chemokine levels compromise alveolar repair, contributing to cigarette smoke-induced alveolar damage and emphysema...
  12. ncbi Neutrophil elastase and cancer
    Takashi Sato
    Department of Otolaryngology, Aichi Gakuin University, Suemori dori 2 11, Chikusa ku 464 8651, Aichi, Japan
    Surg Oncol 15:217-22. 2006
    ..The use of NE inhibitor would seem to be a promising way to prevent the invasion and metastasis of cancer...
  13. pmc Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice
    Kun Shang
    Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
    PLoS ONE 7:e51848. 2012
    ..These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer...
  14. ncbi Transient elevation of neutrophil proteinases in induced sputum during COPD exacerbation
    Helen Ilumets
    Department of Medicine, Division of Pulmonary Medicine, University of Helsinki, Finland
    Scand J Clin Lab Invest 68:618-23. 2008
    ..e., induced sputum, to ascertain whether these proteinases play a role in COPD exacerbation...
  15. ncbi Neutrophils activate macrophages for intracellular killing of Leishmania major through recruitment of TLR4 by neutrophil elastase
    Flavia L Ribeiro-Gomes
    Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
    J Immunol 179:3988-94. 2007
    ..major in draining lymph nodes of TLR4-sufficient, but not TLR4-deficient mice. These results indicate that NE plays a previously unrecognized protective role in host responses to L. major infection...
  16. pmc Neutrophil elastase modulates cytokine expression: contribution to host defense against Pseudomonas aeruginosa-induced pneumonia
    Rym Benabid
    INSERM AVENIR Program, CHU de Reims, Maison Blanche, Reims 51092, France
    J Biol Chem 287:34883-94. 2012
    ..aeruginosa-associated diseases will need to be carefully reassessed. Also, therapeutic strategies aiming at NE inhibition should take into account the physiologic roles of the enzyme...
  17. ncbi Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register
    Christine Bellanne-Chantelot
    Hopital Saint Antoine, Laboratoire de d Embryologie Pathologique et de Cytogénétique, 184 rue du Fbg Saint Antoine, 75012 Paris, France
    Blood 103:4119-25. 2004
    ....
  18. pmc Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis
    David S Grenda
    Division of Oncology, Washington University School of Medicine, St Louis, MO 63110, USA
    Blood 110:4179-87. 2007
    ..Collectively, these data provide strong support for a UPR model of SCN disease pathogenesis and place SCN in a growing list of human diseases caused by misfolded proteins...
  19. pmc Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia
    Philip S Rosenberg
    Biostatistics Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
    Br J Haematol 140:210-3. 2008
    ..96). Patients with either mutant or wild-type ELA2 should be followed closely for leukaemic transformation...
  20. ncbi Neutrophil elastase up-regulates cathepsin B and matrix metalloprotease-2 expression
    Patrick Geraghty
    Pulmonary Research Division, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland
    J Immunol 178:5871-8. 2007
    ..This has important implications for therapeutic intervention in protease-mediated diseases...
  21. ncbi Neutrophil elastase induces MUC5AC mucin production in human airway epithelial cells via a cascade involving protein kinase C, reactive oxygen species, and TNF-alpha-converting enzyme
    Matt X G Shao
    Cardiovascular Research Institute and Departments of Medicine and Physiology, University of California San Francisco, San Francisco, California 94143, USA
    J Immunol 175:4009-16. 2005
    ..We conclude that HNE induces MUC5AC mucin expression via a cascade involving PKC-ROS-TACE in human airway epithelial cells...
  22. ncbi Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions
    Brice Korkmaz
    INSERM U618 Proteases et Vectorisation Pulmonaires, Universite Francois Rabelais, 10 boulevard Tonnelle, BP 3223, 37032 Tours Cedex, France
    Biochimie 90:227-42. 2008
    ..This review focuses on the structural and functional properties of these proteases that may explain their specific biological roles, and facilitate their use as molecular targets for new therapeutic strategies...
  23. pmc Neutrophil elastase in cyclic and severe congenital neutropenia
    Marshall S Horwitz
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
    Blood 109:1817-24. 2007
    ..Nevertheless, mutations in all 3 genes are capable of causing the mislocalization of NE and may also induce the unfolded protein response, suggesting that there might a convergent pathogenic mechanism focusing on NE...
  24. ncbi Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia
    D C Dale
    Divisions of Hematology and Medical Genetics, Department of Medicine and the Markey Molecular Medicine Center, University of Washington School of Medicine, Seattle, WA, USA
    Blood 96:2317-22. 2000
    ..This study indicates that mutations of the gene encoding neutrophil elastase are probably the most common cause for severe congenital neutropenia as well as the cause for sporadic and autosomal dominant cyclic neutropenia...
  25. ncbi Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis
    P Shamamian
    Department of Surgery, S.A. Localio Laboratory for Surgical Research, New York University School of Medicine, New York, New York 10016, USA
    J Cell Physiol 189:197-206. 2001
    ..These findings indicate a novel role for PMN-mediated inflammation in a variety of tissue remodeling processes including tumor invasion and angiogenesis...
  26. ncbi Haemophilus influenzae induces neutrophil necrosis: a role in chronic obstructive pulmonary disease?
    Emma J Naylor
    School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK
    Am J Respir Cell Mol Biol 37:135-43. 2007
    ..However, the infiltrating neutrophils fail to kill the bacteria and instead release tissue-damaging products into the lung as they undergo necrosis. These results may help to explain the clinical picture in COPD...
  27. ncbi Relaxin is a candidate drug for lung preservation: relaxin-induced protection of rat lungs from ischemia-reperfusion injury
    Konstantin Alexiou
    Department of Cardiac Surgery, University of Technology Dresden, Dresden, Germany
    J Heart Lung Transplant 29:454-60. 2010
    ..The potent vasoconstrictor and proinflammatory mediator endothelin (ET)-1 plays a major role in this cascade. This study was conducted to determine whether treatment with relaxin, an anti-inflammatory and vasoactive hormone, prevents IR...
  28. ncbi Leukocyte elastase negatively regulates Stromal cell-derived factor-1 (SDF-1)/CXCR4 binding and functions by amino-terminal processing of SDF-1 and CXCR4
    Agustin Valenzuela-Fernandez
    Unite d Immunologie Virale, INSERM U485 de l Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France
    J Biol Chem 277:15677-89. 2002
    ..Blockade of SDF-1 and CXCR4 proteolysis by the specific leukocyte elastase inhibitor, N-methoxysuccinyl-alanine-alanine-proline-valine-chloromethyl ketone, identified elastase as the ..
  29. ncbi Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of α1-antitrypsin in lung cancer
    Yan Xu
    State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University and Institute of System Biomedicine, Peking University, Beijing 100191, China
    Mol Oncol 6:405-17. 2012
    ....
  30. ncbi Serine protease cathepsin G regulates adhesion-dependent neutrophil effector functions by modulating integrin clustering
    Sofia Z Raptis
    Division of Rheumatology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
    Immunity 22:679-91. 2005
    ..These findings identify an important role for CG in integrin-dependent PMN effector functions that are separate from and downstream of integrin-dependent adhesion...
  31. ncbi Differential effects of apoptotic versus lysed cells on macrophage production of cytokines: role of proteases
    V A Fadok
    Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA
    J Immunol 166:6847-54. 2001
    ..Therefore, the outcome of an inflammatory reaction and the potential immunogenicity of Ags within the damaged cell will be determined by which signals predominate...
  32. ncbi Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study
    Bernhardt G Zeiher
    Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA
    Crit Care Med 32:1695-702. 2004
    ....
  33. ncbi Specific allergens enhance elastase release in stimulated neutrophils from asthmatic patients
    Javier Monteseirín
    Departamento de Medicina, Servicio Regional de Immunología y Alergia, Hospital Universitario Virgen Macarena, Sevilla, Espana
    Int Arch Allergy Immunol 131:174-81. 2003
    ..In addition, we attempted to evaluate the relationship between neutrophil degranulation and lung function of the patients, measured as FEV(1)...
  34. pmc Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide
    Jean Pierre Levesque
    Stem Cell Biology Laboratory, Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia
    J Clin Invest 111:187-96. 2003
    ....
  35. ncbi Neutrophil elastase induces IL-8 gene transcription and protein release through p38/NF-{kappa}B activation via EGFR transactivation in a lung epithelial cell line
    Ippei Kuwahara
    Respiratory Immunology and Asthma Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA
    Am J Physiol Lung Cell Mol Physiol 291:L407-16. 2006
    ..We conclude that NE increases IL-8 transcription through p38/NF-kappaB activation via EGFR transactivation...
  36. ncbi Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase
    A Belaaouaj
    Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 289:1185-8. 2000
    ..coli. These findings define a mechanism of nonoxidative bacterial killing by NE and point to OmpA as a bacterial target in host defense...
  37. ncbi Neutrophil elastase inhibitor attenuates hippocampal neuronal damage after transient forebrain ischemia in rats
    Hiroaki Matayoshi
    Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1 1 1 Minami kogushi, Ube, Yamaguchi, 755 8505 Japan
    Brain Res 1259:98-106. 2009
    ..The results suggest that neutrophil elastase may contribute to neuronal death in hippocampal CA1 following forebrain ischemia and that neutrophil elastase inhibitor attenuates neuronal death...
  38. ncbi Inhibition of human neutrophil elastase by erythromycin and flurythromycin, two macrolide antibiotics
    M Gorrini
    Clinica di Malattie dell'Apparato Respiratorio, Laboratorio di Biochimica e Genetica, IRCCS Policlinico San Matteo, Via Taramelli 5, 27100 Pavia, Italy
    Am J Respir Cell Mol Biol 25:492-9. 2001
    ..From our kinetics data, we therefore conclude that Er acts as an alternate substrate HNE inhibitor, whereas FE acts as an inactivator...
  39. ncbi Limited proteolysis of surfactant protein D causes a loss of its calcium-dependent lectin functions
    M Griese
    The Lung Research Group, Children s Hospital of Ludwig Maximilians University, Lindwurmstrasse 4, D 80337 Munich, Germany
    Biochim Biophys Acta 1638:157-63. 2003
    ..Multimeric SP-D was partially digested by human leukocyte elastase (HLE) dose- and time-dependently...
  40. ncbi The neutrophilic inflammatory phenotype is associated with systemic inflammation in asthma
    Lisa G Wood
    Centre for Asthma and Respiratory Diseases, University of Newcastle, Australia
    Chest 142:86-93. 2012
    ..The role of systemic inflammation in asthma is unclear. The aim of this study was to compare systemic inflammation in subjects with stable asthma, categorized by airway inflammatory phenotype, with healthy control subjects...
  41. ncbi Neutrophil elastase: mediator of extracellular matrix destruction and accumulation
    Felix Chua
    Centre for Respiratory Research, Royal Free and University College London Medical School, Rayne Building, 5 University Street, London WC1E 6JJ, UK
    Proc Am Thorac Soc 3:424-7. 2006
    ....
  42. ncbi G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms
    Marta Donini
    Department of Pathology, Section of General Pathology, University of Verona, Italy
    Blood 109:4716-23. 2007
    ..Thereby, we propose that the treatment with G-CSF is not sufficient to correct all of the functional deficiency of neutrophils, and this might account for the consistent risk of infections observed in SCN patients...
  43. pmc Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice
    Steven D Shapiro
    Department of Pulmonary and Critical Care, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Am J Pathol 163:2329-35. 2003
    ..This study demonstrates a direct role for neutrophil elastase in emphysema and highlights the interdependence of the proteinases and inflammatory cells that mediate lung destruction in response to cigarette smoke...
  44. pmc Neutrophil elastase is needed for neutrophil emigration into lungs in ventilator-induced lung injury
    A Murat Kaynar
    Department of Critical Care Medicine, Scaife Hall 639, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Am J Respir Cell Mol Biol 39:53-60. 2008
    ..NE is required for neutrophil egression from the vasculature into the alveolar space, and interfering with this process leads to neutrophil-related endothelial cell injury...
  45. ncbi Neutrophil elastase induces mucus cell metaplasia in mouse lung
    Judith A Voynow
    Department of Pediatrics, Duke University Medical Center, Box 2994, Durham, NC 27710, USA
    Am J Physiol Lung Cell Mol Physiol 287:L1293-302. 2004
    ..The addition of AAPV-CMK reduced these measures of inflammation to control levels. These experiments suggest that NE proteolytic activity initiates an inflammatory process leading to goblet cell metaplasia...
  46. ncbi Papillon-Lefèvre syndrome: correlating the molecular, cellular, and clinical consequences of cathepsin C/dipeptidyl peptidase I deficiency in humans
    Christine T N Pham
    Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA
    J Immunol 173:7277-81. 2004
    ....
  47. ncbi Neutrophil elastase (NE) and NE inhibitors: canonical and noncanonical functions in lung chronic inflammatory diseases (cystic fibrosis and chronic obstructive pulmonary disease)
    Ali Roghanian
    MRC Centre for Inflammation Research, The Queen s Medical Research Institute, Edinburgh University Medical School, Edinburgh, United Kingdom
    J Aerosol Med Pulm Drug Deliv 21:125-44. 2008
    ..We will review "canonical" and new "noncanonical" functions for these molecules, and more particularly, those pertaining to their role in innate and adaptive immunity (antibacterial activity and biasing of the adaptive immune response)...
  48. ncbi The effect of leukocyte elastase on tissue factor pathway inhibitor
    D A Higuchi
    Department of Medicine, Jewish Hospital, Washington University Medical Center, St Louis, MO 63110
    Blood 79:1712-9. 1992
    ..Human leukocyte elastase (HLE) proteolytically cleaves TFPI between threonine-87 and threonine-88 within the polypeptide that links ..
  49. ncbi Elafin and its precursor trappin-2 still inhibit neutrophil serine proteinases when they are covalently bound to extracellular matrix proteins by tissue transglutaminase
    Nicolas Guyot
    INSERM U618 Protéases et Vectorisation Pulmonaires and IFR 135 Imagerie Fonctionnelle, Universite Francois Rabelais, 10 Bd Tonnellé, BP 3223, 37032 Tours Cedex, France
    Biochemistry 44:15610-8. 2005
    ..trappin-2 (also called pre-elafin) are potent protein inhibitors of neutrophil serine proteases such as leukocyte elastase and proteinase 3. Trappin-2 has unique conserved sequence motifs rich in Gln and Lys residues...
  50. ncbi The role of neutrophil elastase in acute lung injury
    Kazuhito Kawabata
    Minase Research Institute, Ono Pharmaceutical Co, Ltd, 3 1 1 Sakurai, Shimamoto, Mishima, Osaka 618 8585, Japan
    Eur J Pharmacol 451:1-10. 2002
    ..A greater understanding of the role of this enzyme in the pathophysiology of acute lung injury will lead to better treatments for this complicated disease...
  51. ncbi Chemically modified tetracycline prevents the development of septic shock and acute respiratory distress syndrome in a clinically applicable porcine model
    Jay Steinberg
    Department of Surgery, State University of New York Upstate Medical University, Syracuse, New York 13210, USA
    Shock 24:348-56. 2005
    ....
  52. ncbi Neutrophil elastase: path clearer, pathogen killer, or just pathologic?
    Steven D Shapiro
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women s Hospital, Harvard University Medical School, Boston, Massachusetts 02115, USA
    Am J Respir Cell Mol Biol 26:266-8. 2002
  53. pmc Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases
    C A Owen
    Department of Medicine, University of Utah Health Sciences Center, Salt Lake City 84132, USA
    J Cell Biol 131:775-89. 1995
    ..we provide the first report that human neutrophils express persistently active cell surface-bound human leukocyte elastase and cathepsin G on their cell surface...
  54. ncbi Elastase inhibition assay with peptide substrates - an example for the limited comparability of in vitro results
    Inken Groth
    Pharmaceutical Institute, University of Kiel, Kiel, Germany
    Planta Med 74:852-8. 2008
    ..In conclusion, by the choice of the enzyme substrate, both the apparent maximum activity and the IC (50) of an inhibitor can be influenced. Therefore, only results from identical test systems should be compared....
  55. ncbi Inhibition of human leukocyte elastase activity by chondroitin sulfates
    N Volpi
    Department of Biologia Animale, University of Modena, Italy
    Chem Biol Interact 105:157-67. 1997
    ..and devoid of appreciable anticoagulant activity were evaluated for their capacity to inhibit human leukocyte elastase activity in vitro by using a chromogenic substrate...
  56. ncbi Neutrophil elastase up-regulates interleukin-8 via toll-like receptor 4
    James M Devaney
    Respiratory Research, Department of Medicine, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland
    FEBS Lett 544:129-32. 2003
    ..Furthermore, a TLR4 neutralising antibody abrogates NE-induced IL-8 production, and induces tolerance to a secondary lipopolysaccharide stimulus. These data implicate TLR4 in NE induced IL-8 expression in bronchial epithelium...
  57. ncbi Elevated serum concentrations of polymorphonuclear neutrophilic leukocyte elastase in systemic sclerosis: association with pulmonary fibrosis
    Toshihide Hara
    Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1 7 1 Sakamoto, Nagasaki 852 8501, Japan
    J Rheumatol 36:99-105. 2009
    ..To determine the serum concentrations and clinical association of polymorphonuclear neutrophilic leukocyte (PMN) elastase in patients with systemic sclerosis (SSc)...
  58. ncbi Proteolytic cleavage of annexin 1 by human leukocyte elastase
    Ursula Rescher
    Center for Molecular Biology of Inflammation, Institute for Medical Biochemistry, Von Esmarch Strasse 56, 48149 Munster, Germany
    Biochim Biophys Acta 1763:1320-4. 2006
    ..resulted in the truncation of annexin 1, which seemed to depend on the proteolytic activity of human leukocyte elastase (HLE)...
  59. ncbi DNase I acutely increases cystic fibrosis sputum elastase activity and its potential to induce lung hemorrhage in mice
    A M Cantin
    Unite de Recherche Pulmonaire, Centre universitaire de sante de l Estrie, Fluerimont, Quebec, Canada
    Am J Respir Crit Care Med 157:464-9. 1998
    ..We conclude that DNase I therapy of patients with cystic fibrosis can acutely increase the elastase activity of sputum and also its potential to induce hemorrhage in the murine lung...
  60. pmc Human neutrophil elastase-mediated cleavage sites of MMP-9 and TIMP-1: implications to cystic fibrosis proteolytic dysfunction
    Patricia L Jackson
    Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
    Mol Med 16:159-66. 2010
    ..These results demonstrate increased MMP-9 activity in stable CF lung disease, and the presence of specific protease products in CF sputum highlights that HNE-mediated activity plays a role in this dysregulation...
  61. ncbi Human neutrophil elastase inhibitors in innate and adaptive immunity
    P M Fitch
    MRC Centre for Inflammation Research, University of Edinburgh, The Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK
    Biochem Soc Trans 34:279-82. 2006
    ....
  62. ncbi The involvement of nitric oxide, nitric oxide synthase, neutrophil elastase, myeloperoxidase and proinflammatory cytokines in the acute lung injury caused by phorbol myristate acetate
    Yi Ling Yang
    Institute of Biotechnology, National Chia Yi University, Chiayi, Taiwan
    J Biomed Sci 15:499-507. 2008
    ..PMA upregulated the expression of iNOS mRNA. Our results suggest that neutrophil activation by PMA causes release of NE, upregulation of iNOS and a series of inflammatory responses leading to endothelial damage and ALI...
  63. pmc Proteolysis of human thrombin generates novel host defense peptides
    Praveen Papareddy
    Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden
    PLoS Pathog 6:e1000857. 2010
    ..These findings provide a novel link between the coagulation system and host-defense peptides, two fundamental biological systems activated in response to injury and microbial invasion...
  64. ncbi Neutrophil elastase mediates innate host protection against Pseudomonas aeruginosa
    Tim O Hirche
    Institut National de la Sante et de la Recherche Medicale, Programme AVENIR, IFR53, University of Reims Champagne Ardenne, Reims, France
    J Immunol 181:4945-54. 2008
    ..Consistent with this, the use of an isogenic mutant deficient in outer membrane protein F negated the role of NE in host defense against P. aeruginosa infection...
  65. ncbi Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species
    Bernard M Fischer
    Division of Pediatric Pulmonary Diseases, Duke University Medical Center, Durham, North Carolina 27710, USA
    Am J Respir Cell Mol Biol 26:447-52. 2002
    ..NE treatment increased cellular fluorescence in both cell types, indicating generation of intracellular reactive oxygen species. We conclude that NE treatment increases MUC5AC gene expression by an oxidant-dependent mechanism...
  66. pmc Elevated expression of polymorphonuclear leukocyte elastase in breast cancer tissue is associated with tamoxifen failure in patients with advanced disease
    J A Foekens
    Department of Medical Oncology, Erasmus MC Daniel den Hoed, Rotterdam, The Netherlands
    Br J Cancer 88:1084-90. 2003
    Besides a variety of other proteases, polymorphonuclear leukocyte elastase (PMN-E) is also suggested to play a role in the processes of tumour cell invasion and metastasis...
  67. ncbi Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (SSR69071), a novel, orally active elastase inhibitor
    Zoltan Kapui
    Discovery Research, Sanofi Synthelabo Internal Medicine Budapest Site, Chinoin, Sanofi Synthelabo Group, Budapest, Hungary
    J Pharmacol Exp Ther 305:451-9. 2003
    Human leukocyte elastase (HLE) is a proteinase capable of degrading a variety of proteins. Under normal circumstances, the proteolytic activity of HLE is effectively controlled by its natural inhibitors...
  68. pmc Leukocyte elastase induces lung epithelial apoptosis via a PAR-1-, NF-kappaB-, and p53-dependent pathway
    Tomoko Suzuki
    Division of Respirology, Department of Medicine, University of Toronto and Toronto General Hospital Research Institute of the University Health Network, Toronto, Ontario, Canada
    Am J Respir Cell Mol Biol 41:742-55. 2009
    b>Leukocyte elastase induces apoptosis of lung epithelial cells via alterations in mitochondrial permeability, but the signaling pathways regulating this response remain uncertain...
  69. ncbi A novel oral neutrophil elastase inhibitor (ONO-6818) inhibits human neutrophil elastase-induced emphysema in rats
    Takashige Kuraki
    Department of Respiratory Medicine, School of Medicine, Fukuoka University, 7 45 1 Nanakuma, Jonan ku, Fukuoka 814 0180, Japan
    Am J Respir Crit Care Med 166:496-500. 2002
    ..ONO-6818 also inhibited the development of HNE-induced emphysematous changes including lung hyperinflation, degradation of elastic recoil, and airspace enlargement...
  70. ncbi Leukocyte elastase inhibitor: a new regulator of PARP-1
    Chloe Lepretre
    Universite Pierre et Marie Curie Paris 6, Paris, France
    Ann N Y Acad Sci 1171:25-31. 2009
    ..situation in caspase-independent cell death, we investigated the effect of PARP-1 on the acid endonuclease leukocyte elastase inhibitor (LEI)-derived DNase II (L-DNase II)...
  71. ncbi Macrophage interactions with neutrophils regulate Leishmania major infection
    Flavia L Ribeiro-Gomes
    Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
    J Immunol 172:4454-62. 2004
    ..These results indicate that macrophage interactions with dead neutrophils play a previously unrecognized role in host responses to L. major infection...
  72. pmc Analysis of sputum markers in the evaluation of lung inflammation and functional impairment in symptomatic smokers and COPD patients
    Gregorino Paone
    Department of Cardiovascular and Respiratory Sciences, Sapienza University of Rome, S Camillo Forlanini Hospital, Italy
    Dis Markers 31:91-100. 2011
    ..92; for NE 0.81; for IL-8 0.89; for MMP-9 0.81; for HNP, IL-8 and MMP-9 considered together 0.981. The data suggest that the measurement of sputum markers may have an important role in clinical practice for monitoring COPD...
  73. ncbi Neutrophil elastase-mediated killing of bacteria: lessons from targeted mutagenesis
    Abderrazzaq Belaaouaj
    Department of Medicine Pulmonary Division, Washington University School of Medicine, Barnes Jewish Hospital, 660 S Euclid Avenue, Campus Box 8052, St Louis MO 63110, USA
    Microbes Infect 4:1259-64. 2002
    ..Strategies to inhibit NE because of its involvement in tissue-destructive diseases should be reconsidered, while preserving its beneficial properties...
  74. pmc Human neutrophil elastase induces hypersecretion of mucin from well-differentiated human bronchial epithelial cells in vitro via a protein kinase C{delta}-mediated mechanism
    Jin Ah Park
    Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606
    Am J Pathol 167:651-61. 2005
    ..Inhibition of PKCdelta attenuated HNE-mediated mucin secretion. The results suggest HNE stimulation of mucin release by human airway epithelial cells involves intracellular activation of PKC, specifically the delta isoform...
  75. ncbi Do the effects of a protease inhibitor, ulinastatin, on elastase release by blood transfusion depend on interleukin 6?
    T Nishiyama
    Surgical Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    Crit Care Med 29:2106-10. 2001
    Blood transfusion induces polymorphonuclear leukocyte elastase (PMNE) and interleukin 6 (IL-6). IL-6 would activate neutrophils to release PMNE. Ulinastatin, a protease inhibitor, inhibits PMNE release by blood transfusion...
  76. ncbi Decreased neutrophil skin infiltration after UVB exposure in patients with polymorphous light eruption
    Ines J Schornagel
    Department of Dermatology Allergology, University Medical Center Utrecht, Utrecht, The Netherlands
    J Invest Dermatol 123:202-6. 2004
    ..In conclusion, PLE is marked by a decreased skin infiltration of neutrophils after UVB irradiation, possibly leading to a diminished neutrophil-induced suppression...
  77. ncbi The effects of a new human leukocyte elastase inhibitor (recombinant guamerin) on cerulein-induced pancreatitis in rats
    Yun Ju Jo
    Department of Internal Medicine, Eulji University College of Medicine, 280 1 Hagye 1 dong, Nowon Gu, Seoul 139 711, South Korea
    Int Immunopharmacol 8:959-66. 2008
    ..We aimed to investigate the effects and the possible mechanism of a new human leukocyte elastase inhibitor (recombinant guamerin) in the treatment of cerulein-induced acute pancreatitis in rats.
  78. ncbi Degradation of cross-linked fibrin by leukocyte elastase as alternative pathway for plasmin-mediated fibrinolysis in sepsis-induced disseminated intravascular coagulation
    Seiji Madoiwa
    Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
    Thromb Res 127:349-55. 2011
    An alternative pathway for fibrinolysis that comprises leukocyte elastase and its interaction with the plasminogen activator-plasmin system has been suggested...
  79. ncbi The effect of sivelestat sodium on post-cardiopulmonary bypass acute lung injury in a neonatal piglet model
    Makoto Ando
    Department of Pediatric Cardiac Surgery, Sakakibara Heart Institute, Fuchu si, Tokyo, Japan
    Interact Cardiovasc Thorac Surg 7:785-8. 2008
    ..05). Intraoperative administration of sivelestat effectively reduced neutrophil induction and activation in the lung and improved oxygenation after cardiopulmonary bypass in a piglet model...
  80. ncbi Protective effects of a selective neutrophil elastase inhibitor (sivelestat) on lipopolysaccharide-induced acute dysfunction of the pulmonary microcirculation
    Yoshiaki Inoue
    Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    Crit Care Med 33:1814-22. 2005
    ..The purpose of this study was to evaluate the effect of a neutrophil elastase inhibitor, sivelestat, on lipopolysaccharide-induced acute lung injury through analysis of hemodynamic changes in the pulmonary microcirculation...
  81. ncbi Histochemical study of leukocyte elastase activity in alkali-burned rabbit cornea
    J Cejkova
    Department of Eye Histochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Ophthalmic Res 29:154-60. 1997
    In order to contribute to a better understanding of the role of leukocyte elastase in corneal melting after a severe alkali burn, the in situ appearance and activity of this enzyme in the rabbit cornea was examined...
  82. ncbi A neutrophil elastase inhibitor, sivelestat, reduces lung injury following endotoxin-induced shock in rats by inhibiting HMGB1
    Satoshi Hagiwara
    Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, 1 1 Idaigaoka Hasamamachi Yufu, City Oita 879 5593, Japan
    Inflammation 31:227-34. 2008
    ..Furthermore, inhibition of NF-kappaB activity was observed with the administration of sivelestat. These results suggest that sivelestat reduces LPS-induced lung injury at least partially by inhibiting inflammation and NF-kappaB activity...
  83. ncbi Patterns of neutrophil serine protease-dependent cleavage of surfactant protein D in inflammatory lung disease
    Jessica Cooley
    Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA
    J Leukoc Biol 83:946-55. 2008
    ..The findings support a pre-eminent role for neutrophil elastase as the critical protease responsible for SP-D depletion in inflammatory lung disease...
  84. ncbi Plasma and urine leukocyte elastase-alpha1protease inhibitor complex as a marker of early and long-term kidney graft function
    Malgorzata Zynek-Litwin
    Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
    Nephrol Dial Transplant 25:2346-51. 2010
    Neutrophils are mediators of ischaemia/reperfusion (I/R) injury following kidney transplantation (kTx). Leukocyte elastase (LE) complex with alpha(1)protease inhibitor (LE-alpha(1)PI) is a marker of neutrophil degranulation...
  85. ncbi Effect of a neutrophil elastase inhibitor on acute lung injury after cardiopulmonary bypass
    Masahiro Fujii
    Division of Cardiovascular Surgery, Department of Surgery, Nippon Medical School, Tokyo 113 8603, Japan
    Interact Cardiovasc Thorac Surg 10:859-62. 2010
    ..However, sivelestat attenuated the pattern of physiological deterioration of gas exchange. Sivelestat may attenuate neutrophil elastase or proinflammatory cytokines, and improve pulmonary dysfunction in patients undergoing CPB...
  86. ncbi Elastase-released epidermal growth factor recruits epidermal growth factor receptor and extracellular signal-regulated kinases to down-regulate tropoelastin mRNA in lung fibroblasts
    Sandra J DiCamillo
    Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 277:18938-46. 2002
    ..We conclude that proteolytically released EGF signals directly via EGFR and ERK to down-regulate tropoelastin mRNA in NE-challenged lung fibroblasts...
  87. ncbi (-)Epigallocatechin-3-gallate inhibits leukocyte elastase: potential of the phyto-factor in hindering inflammation, emphysema, and invasion
    Luigi Sartor
    Department of Experimental Biomedical Sciences, Medical School of Padova, Italy
    J Leukoc Biol 71:73-9. 2002
    Flavanol (-)epigallocatechin-3-gallate is shown to be a potent natural inhibitor of leukocyte elastase that may be used to reduce elastase-mediated progression to emphysema and tumor invasion...
  88. ncbi Gut luminal neutrophil migration is influenced by the anatomical site of Crohn's disease
    I D Arnott
    University Department of Medical Sciences, Western General Hospital, Edinburgh, UK
    Eur J Gastroenterol Hepatol 13:239-43. 2001
    ..Granulocyte elastase, a neutrophil-bound enzyme, interleukin 8 and 1beta can be detected in whole-gut lavage fluid. We aimed to assess differences between large- and small-bowel Crohn's disease...
  89. ncbi Neutrophil elastase induces cell proliferation and migration by the release of TGF-alpha, PDGF and VEGF in esophageal cell lines
    Yoshiyuki Wada
    Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1 2 3 Kasumi, Minami Ku, Hiroshima 734 8553, Japan
    Oncol Rep 17:161-7. 2007
    ..Furthermore, we postulate that postoperative administration of sivelestat might be useful as a new molecular-targeting cancer therapy as well as for the treatment of postoperative respiratory complications...
  90. ncbi A comparison of the defective granulopoiesis in childhood cyclic neutropenia and in severe congenital neutropenia
    Yasuhiko Sera
    Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, 1 2 3 Kasumi, Minami Ku, Hiroshima 734 8551, Japan
    Haematologica 90:1032-41. 2005
    ..Mutations in the neutrophil elastase gene, ELA2, have been reported in patients with CyN and in those with SCN. We examined granulopoietic defects in CyN patients with those in SCN patients...
  91. ncbi Neutrophil elastase is severely down-regulated in severe congenital neutropenia independent of ELA2 or HAX1 mutations but dependent on LEF-1
    Julia Skokowa
    Department of Molecular Hematopoiesis, Hannover Medical School, Hannover, Germany
    Blood 114:3044-51. 2009
    ..LEF-1 rescue of CD34(+) cells isolated from 2 patients with CN resulted in granulocytic differentiation of the cells which was in line with increased levels of functionally active ELA2/NE...
  92. ncbi Oxidized elafin and trappin poorly inhibit the elastolytic activity of neutrophil elastase and proteinase 3
    Shila M Nobar
    Laboratoire d Enzymologie, INSERM U392, Universite Louis Pasteur de Strasbourg, Illkirch, France
    FEBS J 272:5883-93. 2005
    ..We conclude that in vivo oxidation of elafin and trappin strongly impairs their activity. Inhibitor-based therapy of inflammatory lung diseases must be carried out using oxidation-resistant variants of these molecules...
  93. ncbi Strong evidence for autosomal dominant inheritance of severe congenital neutropenia associated with ELA2 mutations
    Laurence A Boxer
    Divison of Pediatric Hematology Oncology, Department of Pediatrics, C S Mott Children s Hospital, University of Michigan, Ann Arbor, Michigan 48109 0238, USA
    J Pediatr 148:633-6. 2006
    ..To investigate cases of severe congenital neutropenia (SCN) to ascertain SCN inheritance after determining that the same sperm donor was used by 4 different families to impregnate mothers...
  94. ncbi Enhanced matrix-degrading proteolytic activity within the thin thrombus-covered wall of human abdominal aortic aneurysms
    Ireneusz Wiernicki
    Department of Vascular Surgery and Angiology, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70 111 Szczecin, Poland
    Atherosclerosis 212:161-5. 2010
    ..In the present study the hypothesis that thin thrombus is associated with enhanced proteolytic activity within human AAA wall was investigated...
  95. ncbi Characterization of T(4)-binding globulin cleaved by human leukocyte elastase
    Onno E Janssen
    Department of Medicine, University of Essen, D 45122 Essen, Germany
    J Clin Endocrinol Metab 87:1217-22. 2002
    ..Cleavage of corticosteroid-binding globulin by human leukocyte elastase results in the reduction of its hormone-binding affinity and capacity...
  96. ncbi Cytokines regulate membrane-bound leukocyte elastase on neutrophils: a novel mechanism for effector activity
    C A Owen
    Department of Medicine, University of Utah Health Sciences Center, Salt Lake City 84132, USA
    Am J Physiol 272:L385-93. 1997
    Membrane-bound leukocyte elastase activity on neutrophils may have potent proinflammatory effects...
  97. ncbi Molecular screening of the neutrophil elastase gene in congenital neutropenia
    M Thomas
    Department of Hematology, Christian Medical College, Vellore, Tamil Nadu, India
    Indian Pediatr 43:1081-4. 2006
    ..Pathogenesis of congenital neutropenia can now be attributed to mutations of the ELA2 gene encoding neutrophil elastase. A child with severe congenital neutropenia with a heterozygous mutation G1887A in exon 2 of ELA2 gene is reported...
  98. ncbi Ela2 mutations and clinical manifestations in familial congenital neutropenia
    Masaaki Shiohara
    Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan
    J Pediatr Hematol Oncol 31:319-24. 2009
    ..The contents of the neutrophil-specific granule proteins cathelicidin antimicrobial peptide and neutrophil gelatinase-associated lipocalin were also analyzed in SCN...
  99. ncbi Dysregulation of transcriptions in primary granule constituents during myeloid proliferation and differentiation in patients with severe congenital neutropenia
    Hiroshi Kawaguchi
    Department of Pediatrics, Hiroshima University School of Medicine, Hiroshima University, Higashi Hiroshima, Japan
    J Leukoc Biol 73:225-34. 2003
    ..We hypothesize that the abnormal regulation of the transcription in primary granule constituents might involve the defective proliferation and differentiation of myeloid cells in patients with SCN...
  100. ncbi Shed syndecan-1 restricts neutrophil elastase from alpha1-antitrypsin in neutrophilic airway inflammation
    Stanley C H Chan
    Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China
    Am J Respir Cell Mol Biol 41:620-8. 2009
    ..We conclude that the HS moiety of shed Syn-1 binds and restricts NE from inhibition by alpha(1)-AT...
  101. ncbi Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia
    Stephen J Salipante
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    Hum Mutat 28:874-81. 2007
    ....

Research Grants57

  1. Sulfated Polysaccharide Derivatives for the Treatment of Rosacea
    NARAYANAM RAO; Fiscal Year: 2009
    ..activities at nanogram/ml concentrations, including inhibition of the cationic PMN protease human leukocyte elastase (HLE) and inhibition of the PMN adhesion receptor P-selectin...
  2. Sulfated Polysaccharide Derivatives for Treatment of Macular Degeneration
    Jianxing Zhang; Fiscal Year: 2009
    ..at nanogram/ml concentrations, including inhibition of complement activation, P-selectin and human leukocyte elastase (HLE)...
  3. ALPHA-1-PROTEINASE INHIBITOR DEFICIENCY AND EMPHYSEMA
    Savio Woo; Fiscal Year: 1990
    ..is to defuse into the lung and protect this important organ from destruction by excessive polymorphonuclear leukocyte elastase. Genetic deficiency of Alpha1-antitrypsin predisposes affected individuals to development of chronic ..
  4. PULMONARY EMPHYSEMA--ROLE OF SERINE PROTEINASES
    John Hoidal; Fiscal Year: 2000
    ..leukocytes in lung health and disease, focusing, in particular, on the involvement proteinase 3 (PR-3) and leukocyte elastase (LE) in the pathogenesis of emphysema...
  5. ALLENES OF SYNTHETIC AND BIOCHEMICAL IMPORTANCE
    JOHN BUYNAK; Fiscal Year: 1993
    ..b>Leukocyte elastase is overactive in patients with emphysema and in those with rheumatoid arthritis...
  6. Mistargeting of Elastase in Bone Marrow Failure
    Marshall Horwitz; Fiscal Year: 2008
    ..1 Determine if ELA2 promoter variation contributes to neutropenia; 3.2 Measure the frequency of the ELA2 C-199A allele in individuals of African descent with benign ethnic neutropenia; 3.3 Identify new neutropenia genes. ..
  7. Collagenolysis and Elastolysis in Urinary Incontinence
    Bertha Chen; Fiscal Year: 2008
    ..Our goal is to identify specific pathophysiologic changes related to reproductive events and aging which underlie the development of SUI as a first step to identifying potential targets for therapeutic intervention. ..
  8. REGULATION OF MUCIN GENE EXPRESSION BY ELASTASE
    Judith Voynow; Fiscal Year: 2003
    ..The ultimate goal is to use information from this project to identify new biologic targets for therapeutic interventions to prevent mucus obstruction in chronic inflammatory airway diseases. ..
  9. Mucin Gene Regulation by Elastase and Oxidants
    Judith Voynow; Fiscal Year: 2008
    ..b. To determine whether NE and/or NQO1-generated ROS affect HuR binding to MUC5AC. c. To determine whether HuR binding is sufficient for MUC5AC mRNA stabilization. ..
  10. MUC4 Mucin and Airway Epithelial Regeneration in COPD
    Judith Voynow; Fiscal Year: 2006
    ..Our ultimate goal is to use information from this project to identify new biologic targets for rational therapies to induce normal airway epithelial proliferation and differentiation following injury. ..
  11. IgA1-Regulation of Complement in Periodontal Disease
    ROBERT BOACKLE; Fiscal Year: 2002
    ....
  12. Molecular Studies of Severe Congenital Neutropenia
    Andrew Aprikyan; Fiscal Year: 2005
    ..These models will be useful for development of novel therapeutic strategies for treatment of severe congenital neutropenia and prevention of its evolution to acute myeloid leukemia. ..
  13. Complement-fixing Bi-Specific Antibodies Against HIV-1
    ROBERT BOACKLE; Fiscal Year: 2007
    ..Our third objective is to evaluate the complement-mediated neutralization of infectious HIV-1 particles by paired combinations of the truncated bi-specific antibodies. [unreadable] [unreadable] [unreadable]..
  14. REGULATION OF POLYMORPHONUCLEAR LEUKOCYTE PHAGOCYTOSIS
    Laurence Boxer; Fiscal Year: 2003
    ..Specific AIM 3 will examine the cellular targets of ceramide and sphingosine actin during PMN phagocytosis, focusing primarily on activation of mitogen-activated kinase (MAPK), Raf kinase and how they are linked to phagosome generation. ..
  15. Ion Transport and Mucus Clearance in CF Airways
    Robert Tarran; Fiscal Year: 2007
    ..Based on these observations, the specific aims of this proposal are (1) to identify sensors of ASL volume, (2) to understand how ASL volume regulation is transduced and (3) to normalize CF airway surface liquid volume regulation. ..
  16. Noninvasive biomarkers of proteolytic activity in CF
    Scott Sagel; Fiscal Year: 2007
    ..In addition, he will actively participate and train in the Pediatric GCRC, and frequently interact with his sponsor, mentors, and collaborators. ..
  17. Role of DPPI & Serine Proteases in Inflammatory Diseases
    Christine Pham; Fiscal Year: 2007
    ..We also hypothesize that decreased expression of complement regulators in the kidney mav be a determinant that influences the severity of tissue damage in the target organ. ..
  18. A Novel & Tailorable Topical Wound Therapy Based on a Semi-Interpenetrating Polym
    DAVID VACHON; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  19. Infrared spectroscopy as a novel diagnostic tool for periodontitis
    David Scott; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  20. Phase 2 study of VX-770 in Cystic Fibrosis Subjectswith G551D
    CLAUDIA ORDONEZ; Fiscal Year: 2007
    ..These effects may help preserve pulmonary function, decrease morbidity associated with progressive lung impairment/damage, and prolong survival in CF patients. [unreadable] [unreadable] [unreadable]..
  21. Epithelial Cell Cycle Regulation by Elastase
    Bernard Fischer; Fiscal Year: 2008
    ..The information derived from these experiments will provide fundamental insights into epithelial response to injury, and provide a foundation to investigate normal epithelial regeneration versus pathologic remodeling. ..
  22. Innate Immunity and exacerbations of COPD
    Sanjay Sethi; Fiscal Year: 2009
    ..The overall goal of this research is to identify specific aspects of the innate defense of the lung that determine the frequency of exacerbations in COPD that will serve as potential therapeutic targets to reduce exacerbations. ..
  23. Delivering antiproteases to the bronchiectatic airway
    Thomas Ferkol; Fiscal Year: 2009
    ....
  24. Alpha-1 AD Carriers and Lung Cancer Risk
    Ping Yang; Fiscal Year: 2009
    ..abstract_text> ..
  25. ISLET OF LANGERHANS GRAFT MONITORING BY MAGNETIC RESONANCE IMAGING
    Thierry Berney; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  26. Topical Modulation of Burn Wound Healing
    DAVID VACHON; Fiscal Year: 2008
    ..These basic mechanisms will also apply to chemical burns and radiation induced injury, as well as other inflammatory diseases of the skin. [unreadable] [unreadable] [unreadable]..
  27. Health and QOL among Long-Term Lung Cancer Survivors
    Ping Yang; Fiscal Year: 2010
    ....
  28. Growth Factors in Vascular Biology
    MATTHEW NUGENT; Fiscal Year: 2008
    ..These studies will have wide ranging impact on vascular biology and will likely reveal previously undefined mechanisms of growth factor control that could help identify targets for clinical modulation. ..
  29. Peptide-Modified Sulfonated Styrene Block Copolymers for Vascular Applications
    DAVID VACHON; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  30. Epigenetic Markers for Lung Cancer Detection
    Jong Park; Fiscal Year: 2006
    ..The proposed study will generate data that will be the groundwork for larger studies to validate the use of the identified methylation sites to develop markers for early lung cancer diagnosis. ..
  31. Osteopontin and Molecular Mechanisms of Bone Metastasis
    Susan Rittling; Fiscal Year: 2006
    ..Together, these experiments will provide important data to establish the mechanism of bone metastasis by a novel cell line and define the role of host OPN and TGF-beta as potential therapeutic targets. ..
  32. Nuclear Localization of Heparan Sulfate Proteoglycans
    MATTHEW NUGENT; Fiscal Year: 2004
    ..Information from these studies could provide the foundation for the development of a new generation of therapies aimed at facilitating corneal repair without scarring...
  33. GENETIC REGULATION OF 03-INDUCED INFLAMMATION
    W Foster; Fiscal Year: 2003
    ..abstract_text> ..
  34. MARROW REGULATION IN CYCLIC HEMATOPOIESIS
    David Dale; Fiscal Year: 2003
    ....
  35. PHOSPHATIDYLSERINE-SPECIFIC RECEPTOR FOR APOPTOTIC CELLS
    Valerie Fadok; Fiscal Year: 2004
    ..The investigators hypothesize that PS recognition has been preserved throughout phylogeny as an effective mechanism mediating the removal of apoantibodies. ..
  36. THE ROLE OF ALPHA-DEFENSINS IN CYSTIC FIBROSIS LUNG DISE
    L Spencer; Fiscal Year: 2004
    ..Following completion of this training and research, my long-term career interest will remain in the area of pathogenesis and applied clinical intervention of neutrophil-mediated pulmonary disease in pediatric patients. ..
  37. Elucidation of epoxide hydrolase polymorphisms
    Jong Park; Fiscal Year: 2002
    ....
  38. Targeted Delivery of Interleukin-10
    Thomas Ferkol; Fiscal Year: 2004
    ..abstract_text> ..
  39. NEUTROPHIL RECRUITMENT IN LPS-INDUCED AIRWAY DISEASE
    Jessica Moreland; Fiscal Year: 2004
    ....
  40. INHIBITORS OF PROTEOLYTIC ENZYMES
    WILLIAM GROUTAS; Fiscal Year: 2005
    ....
  41. 2005 Elastin and Elastic Fibers Gordon Conference
    CATHERINE KIELTY; Fiscal Year: 2005
    ..As in past years, these personal interactions will result in new collaborative studies and stimulate novel avenues of elastic fiber investigation. ..
  42. Genetic variants of primary ciliary dyskinesia
    Thomas Ferkol; Fiscal Year: 2006
    ..Using this approach, we will define the genetic spectrum of PCD, and correlate specific genetic variants with clinical presentations of this disease, especially during the neonatal period. ..
  43. ENHANCING COLLECTIN MEDIATED HOST DEFENSE
    Kevan Hartshorn; Fiscal Year: 2001
    ..These experiments should yield important insights into basic collection biology and demonstrate that enhancement of collectin-mediated pulmonary host defense can be achieved in vivo through rational alteration of wild type collectins. ..
  44. The Mechanism of IVIG Action in Pemphigus
    Zhi Liu; Fiscal Year: 2006
    ..The overall goal of this project is to study the mechanisms of WIG action in autoantibody-mediated diseases and develop novel therapies to replace current immunosuppressive treatments, which confer severe side effects. ..
  45. P aeruginosa virulence in cystic fibrosis lung disease
    CLAUDIA ORDONEZ; Fiscal Year: 2006
    ..aeruginosa virulence factors in CF that may be important targets for new therapies with the potential to decrease disease-specific morbidity and mortality in CF. ..
  46. CITRIC ACID CYCLE METABOLISM DURING CARDIAC SURGERY
    Michael Jessen; Fiscal Year: 2001
    ..This, in turn, should lead to improvements in cardioplegic solutions currently used. ..
  47. Serine-Protease Effects on the Epithelial Sodium Channel
    Ray Caldwell; Fiscal Year: 2006
    ..Collectively, these components will be vital for him to emerge as an independent investigator [unreadable] [unreadable]..
  48. REGULATION OF INTESTINAL EPITHELIAL CHEMOKINE SECRETION
    Andrew Gewirtz; Fiscal Year: 2002
    ..In addition to containing an extensive array of basic research equipment, this lab space contains a new thermostatted spectrofluorimeter to be used primarily by Dr. Gewirtz. ..
  49. Dependency of O-3 Induced Lung Mucus Hypersecretion on NQ01
    W Michael Foster; Fiscal Year: 2010
    ....
  50. Synthesis and Processing of Sulfonated Block Copolymer Biomaterials
    DAVID VACHON; Fiscal Year: 2006
    ..This Phase I proposal addresses key needs for the expansion of Aegis' materials into a growing healthcare marketplace. [unreadable] [unreadable] [unreadable]..
  51. PROTEASE MODULATING WOUND DRESSINGS FOR THE TREATMENT OF VENOUS ULCERS
    DAVID VACHON; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  52. A Novel & Tailorable Drug Delivery Device for the Treatment of Periodontitis
    DAVID VACHON; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  53. Novel Wound Dressing for Chronic Ulcers
    DAVID VACHON; Fiscal Year: 2002
    ..abstract_text> ..
  54. HAEMOPHILUS ANTIGEN REGULATION OF INFLAMMATION IN COPD
    Sanjay Sethi; Fiscal Year: 2003
    ..Identification of the integral bacterial and host components that contribute to immune-mediated inflammation in COPD will ultimately lead to novel therapeutic strategies to alter disease progression and improve outcome in COPD. ..
  55. Novel Cation-Exchange Wound Dressing for Diabetic Ulcers
    DAVID VACHON; Fiscal Year: 2004
    ....
  56. Role of CIC-3 channels in regulation of cell volume and shape in neutrophils
    Jessica Moreland; Fiscal Year: 2007
    ..The studies proposed will advance our fundamental knowledge of the function of neutrophils in the maintenance of normal immune system function. [unreadable] [unreadable] [unreadable]..