Polymorphonuclear leukocytes have been implicated in connective tissue injury in a variety of disease processes. To gain insight into mechanisms by which neutrophils might degrade connective tissue macromolecules in the presence of proteinase inhibitors, we have used a model system that allows neutrophils to be held in vitro under physiologic conditions in close proximity to a very proteinase-sensitive substrate, 125I-labeled fibronectin. We have found: (a) neutrophils spread rapidly on the fibronectin substrate; (b) fibronectin proteolysis by neutrophils is largely attributable to released elastase, and is linearly related to cell number over the range of 2,000 to 30,000 cells per assay; (c) oxidants released from neutrophils stimulated by opsonized zymosan or phorbol myristate acetate do not protect released elastase from inhibition by α1-proteinase inhibitor or α2-macroglobulin; (d) neutrophil myeloperoxidase and enzymatically generated superoxide anion render α1-proteinase inhibitor ineffective against fibronectin proteolysis when neutrophils are added 30 min later; and (e) α1-proteinase inhibitor and α2-macroglobulin incompletely inhibit fibronectin proteolysis by neutrophils (79.8±6.3 and 73.5±12.0%, respectively.) The data suggested that proteolysis due to neutrophils that are in contact with susceptible macromolecules may occur due to partial exclusion of inhibitors from the cell-substrate interface. Although confirming that α1-proteinase inhibitor is ineffective against neutrophil-derived proteolysis after exposure to oxidants, these studies did not support the hypothesis that oxidants released from stimulated neutrophils enhance activity of proteinases they release in the presence of α1-proteinase inhibitor. We anticipate that further studies with this test system will be helpful in defining conditions that modulate inflammatory connective tissue injury in diseases such as pulmonary emphysema and rheumatoid arthritis.
Edward J. Campbell, Robert M. Senior, John A. McDonald, David L. Cox, Jeanne M. Greco, Jill A. Landis
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Evidence that infiltrating neutrophils do not release reactive oxygen species in the site of spinal cord injury
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Experimental Neurology | 2004 |
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New England Journal of Medicine | 2000 |
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Alimentary Pharmacology & Therapeutics | 1999 |
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American journal of respiratory and critical care medicine | 1999 |
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The Journal of laboratory and clinical medicine | 1999 |
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Critical Care Medicine | 1999 |
Molecular Biology of the Lung
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Respirology | 1997 |
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Journal of Neurosurgery | 1997 |
DISCREPANCY BETWEEN LATEX AND ELISA D-DIMER VALUES IN SEPSIS MAY BE CAUSED BY HUMAN NEUTROPHIL ELASTASE
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Critical Care Medicine | 1997 |
Rebamipide attenuates indomethacin-induced gastric mucosal lesion formation by inhibiting activation of leukocytes in rats
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Digestive Diseases and Sciences | 1997 |
Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver
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Digestive Diseases and Sciences | 1996 |
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Australian and New Zealand Journal of Medicine | 1996 |
Pulmonary vascular injury induced by hemorrhagic shock is mediated by P-selectin in rats
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Thrombosis Research | 1996 |
D-dimers are degraded by human neutrophil elastase
ET Bach-Gansmo, S Halvorsen, HC Godal, OH Skjønsberg |
Thrombosis Research | 1996 |
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Critical Care Medicine | 1996 |
ARDS Acute Respiratory Distress in Adults
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1996 | |
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Experimental Lung Research | 1995 |
Clinical Implications of Gene Therapy for Alpha1-Antitrypsin Deficiency
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Fibrin regulates neutrophil migration in response to interleukin 8, leukotriene B4, tumor necrosis factor, and formyl-methionyl-leucyl- phenylalanine
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Journal of Experimental Medicine | 1995 |
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Digestive Diseases and Sciences | 1994 |
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European Journal of Biochemistry | 1994 |
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British Journal of Surgery | 1994 |
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Kidney International | 1994 |
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Infection and immunity | 1994 |
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Thorax | 1994 |
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Thorax | 1994 |
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The Journal of Cell Biology | 1993 |
Chemical, biochemical, pharmacokinetic, and biological properties of L-680,833: a potent, orally active monocyclic beta-lactam inhibitor of human polymorphonuclear leukocyte elastase
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Proceedings of the National Academy of Sciences | 1993 |
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Bioorganic & Medicinal Chemistry Letters | 1993 |
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American journal of respiratory cell and molecular biology | 1993 |
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Proteases, Protease Inhibitors and Protease-Derived Peptides
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1993 | |
Plasma levels of elastase-specific fibrinopeptides correlate with proteinase inhibitor phenotype. Evidence for increased elastase activity in subjects with homozygous and heterozygous deficiency of alpha 1-proteinase inhibitor
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Journal of Clinical Investigation | 1992 |
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Biochemical Journal | 1992 |
The Role of Protected Extracellular Compartments in Interactions between Leukocytes, and Platelets, and Fibrin/Fibrinogen Matrices
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Annals of the New York Academy of Sciences | 1992 |
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Modern Methods in Protein Nutrition and Metabolism
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Modern Methods in Protein Nutrition and Metabolism | 1992 |
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Arteriosclerosis Thrombosis and Vascular Biology | 1992 |
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Circulation research | 1992 |
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1992 | |
Activated human peripheral blood neutrophils produce epithelial injury and fibronectin breakdown in vitro
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Thorax | 1992 |
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1992 | |
Biochemistry of Inflammation
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1992 | |
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The Clinical Investigator | 1992 |
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Annals of the New York Academy of Sciences | 1991 |
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Annals of the New York Academy of Sciences | 1991 |
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Arthritis & Rheumatism | 1991 |
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Revue Française d'Allergologie et d'Immunologie Clinique | 1991 |
Extracellular Proteolysis of Fibronectin by Neutrophils: Characterization and the Effects of Recombinant Cytokines
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American journal of respiratory cell and molecular biology | 1991 |
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1991 | |
Differential patterns of PMN-elastase and type III procollagen peptide in knee joint effusions due to acute and chronic sports injuries
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Journal of Clinical Investigation | 1990 |
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Free radical biology & medicine | 1990 |
The handling of inhaled antigen within the respiratory tract
RL Clancy, AW Cripps |
Advanced Drug Delivery Reviews | 1990 |
CAP 37, A 37 kD human neutrophil granule cationic protein shares homology with inflammatory proteinases
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Life Sciences | 1990 |
Inhibition of Human Leukocyte Elastase Bound to Elastin: Relative Ineffectiveness and Two Mechanisms of Inhibitory Activity
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American journal of respiratory cell and molecular biology | 1990 |
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American journal of physiology. Cell physiology | 1990 |
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Circulation | 1990 |
Gelenkzerstörung bei entzündlichen rheumatischen Erkrankungen
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1990 | |
Regulation of Proteolysis at the Neutrophil-Substrate Interface by Secretory Leukoprotease Inhibitor
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Science | 1990 |
An evaluation of the neutrophil as a mediator of in vivo renal ischemic-reperfusion injury
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The American Journal of Pathology | 1989 |
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E Remold-O'Donnell, JC Nixon, RM Rose |
Journal of Experimental Medicine | 1989 |
Neutrophil activation by surface bound IgG is via a pertussis toxin insensitive G protein
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Biochemical and Biophysical Research Communications | 1989 |
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Fibronection | 1989 |
Southwestern Internal Medicine Conference: Adult Respiratory Distress Syndrome
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The American Journal of the Medical Sciences | 1989 |
Novel inhibitors of human leukocyte elastase and cathepsin G. Sequence variants of squash seed protease inhibitor with altered protease selectivity
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Biochemistry | 1989 |
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Fundamental Aspects of Cancer
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1989 | |
Oxidative cross-linking of immune complexes by human polymorphonuclear leukocytes
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Ascorbic acid neutralizes reactive oxidants released by hyperactive phagocytes from cigarette smokers
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Membrane and matrix localization of proteinases: a common theme in tumor cell invasion and angiogenesis
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Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | 1988 |
Pericellular proteolysis by neutrophils in the presence of proteinase inhibitors: effects of substrate opsonization
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The Journal of Cell Biology | 1988 |
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FEBS Letters | 1988 |
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PA Vincent, PJ Vecchio, TM Saba |
Experimental and Molecular Pathology | 1988 |
The Respiratory Burst and Its Physiological Significance
AJ Sbarra, RR Strauss |
1988 | |
Degradation of connective tissue components by lung derived leucocytes in vitro: role of proteases and oxidants
GM Brown, K Donaldson |
Thorax | 1988 |
Chronic Bronchitis: The Antiproteinase/Proteinase Balance and the Effect of Infection and Corticosteroids
RA Stockley |
Clinics in Chest Medicine | 1988 |
Experimental arthritis in C57black/6 normal and beige (Chediak-Higashi) mice: in vivo and in vitro observations on cartilage degradation.
Schalkwijk J, Joosten LA, van den Berg WB, van de Putte LB |
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Conditioned medium from stimulated mononuclear leucocytes potentiates the ability of human neutrophils to damage human articular cartilage.
Bates EJ, Kowanko IC, Ferrante A |
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Alpha-1-antitrypsin and the pathogenesis of emphysema
RA Stockley |
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Neutrophil-mediated Vascular Injury
JM Harlan |
Acta Medica Scandinavica | 1987 |
NEUTROPHILS FROM SUBJECTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASE SHOW ENHANCED CHEMOTAXIS AND EXTRACELLULAR PROTEOLYSIS
D Burnett, SL Hill, A Chamba, RA Stockley |
The Lancet | 1987 |
Injury to endothelial cells by phagocytosing polymorphonuclear leukocytes and modulatory role of lipoxygenase products
CM Vandenbroucke-Grauls, HM Thijssen, KP van Kessel, BS van Asbeck, J Verhoef |
Infection and immunity | 1987 |
Elastase-mediated fibrinogenolysis by chemoattractant-stimulated neutrophils occurs in the presence of physiologic concentrations of antiproteinases
JI Weitz, AJ Huang, SL Landman, SC Nicholson, SC Silverstein |
Journal of Experimental Medicine | 1987 |
The antioxidant action of human extracellular fluids. Effect of human serum and its protein components on the inactivation of alpha 1-antiproteinase by hypochlorous acid and by hydrogen peroxide
M Wasil, B Halliwell, DC Hutchison, H Baum |
Biochemical Journal | 1987 |
Mechanism of prostaglandin E2 inhibition of acute changes in vascular permeability
KR McLeish, SR Wellhausen, GT Stelzer |
Inflammation | 1987 |
A low molecular weight, heat-labile factor enhances neutrophil fc receptor–mediated lysosomal enzyme release and phagocytosis
WD Blackburn, LW Heck, WJ Koopman, HD Gresham |
Arthritis & Rheumatism | 1987 |
Extracellular Matrix Injury during Lung Inflammation
EJ Campbell, R M., HG Welgus |
Chest | 1987 |
Increased uptake of monocyte-treated low density lipoproteins by aortic endothelium in vivo
P Görög, VV Kakkar |
Atherosclerosis | 1987 |
Neutrophil-mediated injury to endothelial cells. Enhancement by endotoxin and essential role of neutrophil elastase
LA Smedly, MG Tonnesen, RA Sandhaus, C Haslett, LA Guthrie, RB Johnston, PM Henson, GS Worthen |
Journal of Clinical Investigation | 1986 |
Oxidative regulation of neutrophil elastase-alpha-1-proteinase inhibitor interactions
PJ Ossanna, ST Test, NR Matheson, S Regiani, SJ Weiss |
Journal of Clinical Investigation | 1986 |
Development of an assay for in vivo human neutrophil elastase activity. Increased elastase activity in patients with alpha 1-proteinase inhibitor deficiency
JI Weitz, SL Landman, KA Crowley, S Birken, FJ Morgan |
Journal of Clinical Investigation | 1986 |
Immunolocalization of elastase in human emphysematous lungs
VV Damiano, A Tsang, U Kucich, WR Abrams, J Rosenbloom, P Kimbel, M Fallahnejad, G Weinbaum |
Journal of Clinical Investigation | 1986 |
Neutrophil-induced injury of rat pulmonary alveolar epithelial cells
RH Simon, PD DeHart, RF 3rd |
Journal of Clinical Investigation | 1986 |
The Effect of Catalase and Methionine-S-oxide Reductase on Oxidised α1-Proteinase Inhibitor
HM MORRISON, D BURNETT, RA STOCKLEY |
Biological Chemistry Hoppe-Seyler | 1986 |
Plasma elastase levels in the adult respiratory distress syndrome
LM Zheutlin, EJ Thonar, ER Jacobs, ME Hanley, RA Balk, RC Bone |
Journal of Critical Care | 1986 |
The generation of utilization of chlorinated oxidants by human neutrophils
ST Test, SJ Weiss |
Advances in Free Radical Biology & Medicine | 1986 |
Induction of neutrophil enzyme release by rheumatoid factors: Evidence for differences based on molecular characteristics
WD Blackburn, WJ Koopman, RE Schrohenloher, LW Heck |
Clinical Immunology and Immunopathology | 1986 |
Regulation of Matrix Accumulation
JJ Jeffrey |
Regulation of Matrix Accumulation | 1986 |
Human neutrophil elastase modulates platelet function by limited proteolysis of membrane glycoproteins
MS Brower, RI Levin, K Garry |
Journal of Clinical Investigation | 1985 |
Regulation of alpha 1 proteinase inhibitor function by rabbit alveolar macrophages. Evidence for proteolytic rather than oxidative inactivation
MJ Banda, EJ Clark, Z Werb |
Journal of Clinical Investigation | 1985 |
Sialic acid moieties on surface glycoproteins protect endothelial cells from proteolytic damage
P Göröug, JD Pearson |
The Journal of Pathology | 1985 |
Dissociation of the chemotactic and mitogenic activities of platelet-derived growth factor by human neutrophil elastase
R M, JS Huang, GL Griffin, TF Deuel |
The Journal of Cell Biology | 1985 |
Mechanisms of Cancer Metastasis
KV Honn, WE Powers, BF Sloane |
1985 | |
Bronchoalveolar Lavage in Patients with the Adult Respiratory Distress Syndrome
S Idell, AB Cohen |
Clinics in Chest Medicine | 1985 |
Degradation of fibrin and elastin by intact human alveolar macrophages in vitro. Characterization of a plasminogen activator and its role in matrix degradation
HA Chapman, OL Stone, Z Vavrin |
Journal of Clinical Investigation | 1984 |
Neutrophils degrade subendothelial matrices in the presence of alpha-1-proteinase inhibitor. Cooperative use of lysosomal proteinases and oxygen metabolites
SJ Weiss, S Regiani |
Journal of Clinical Investigation | 1984 |
Effects of neutrophil elastase and other proteases on porcine aortic endothelial prostaglandin I2 production, adenine nucleotide release, and responses to vasoactive agents
EC LeRoy, A Ager, JL Gordon |
Journal of Clinical Investigation | 1984 |
Ecology of Wound Healing in the Oral Cavity
GT Gustafson |
Scandinavian Journal of Haematology | 1984 |
Studies on the fibronectin receptors of human peripheral blood leukocytes. Morphologic and functional characterization
CG Pommier, J O'Shea, T Chused, K Yancey, MM Frank, T Takahashi, EJ Brown |
Journal of Experimental Medicine | 1984 |
Effect of acute plasma fibronectin depletion on tissue fibronectin levels: Analysis by a new fluorescent immunoassay
TM Saba, E Cho, FA Blumenstock |
Experimental and Molecular Pathology | 1984 |
Hemostatic Mechanisms and Metastasis
KV Honn, BF Sloane |
1984 | |
Cysteine proteinases and metastasis
BF Sloane, KV Honn |
Cancer and Metastasis Reviews | 1984 |
Nicotine is Chemotactic for Neutrophils and Enhances Neutrophil Responsiveness to Chemotactic Peptides
N Totti, KT McCusker, EJ Campbell, GL Griffin, RM Senior |
Science | 1984 |
Cleavage and inactivation of Factor IX by granulocyte elastase
A Takaki, DL Enfield, AR Thompson |
Journal of Clinical Investigation | 1983 |
Pathogenesis of Emphysema
JR Hoidal, DE Niewoehner |
Chest | 1983 |
Neutral Proteinases from Human Inflammatory Cells: A Critical Review of Their Role in Extracellular Matrix Degradation
RM Senior, EJ Campbell |
Clinics in Laboratory Medicine | 1983 |
International Review of Connective Tissue Research
JP Ayer |
International Review of Connective Tissue Research | 1964 |