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Citations to this article

Proteolysis by Neutrophils: RELATIVE IMPORTANCE OF CELL-SUBSTRATE CONTACT AND OXIDATIVE INACTIVATION OF PROTEINASE INHIBITORS IN VITRO
Edward J. Campbell, … , Jeanne M. Greco, Jill A. Landis
Edward J. Campbell, … , Jeanne M. Greco, Jill A. Landis
Published October 1, 1982
Citation Information: J Clin Invest. 1982;70(4):845-852. https://doi.org/10.1172/JCI110681.
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Proteolysis by Neutrophils: RELATIVE IMPORTANCE OF CELL-SUBSTRATE CONTACT AND OXIDATIVE INACTIVATION OF PROTEINASE INHIBITORS IN VITRO

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Abstract

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.

Authors

Edward J. Campbell, Robert M. Senior, John A. McDonald, David L. Cox, Jeanne M. Greco, Jill A. Landis

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RH Goldfarb
1989
Oxidative cross-linking of immune complexes by human polymorphonuclear leukocytes
HE Jasin
Journal of Clinical Investigation 1988
Ascorbic acid neutralizes reactive oxidants released by hyperactive phagocytes from cigarette smokers
R Anderson, AJ Theron, GJ Ras
Lung 1988
Membrane and matrix localization of proteinases: a common theme in tumor cell invasion and angiogenesis
D Moscatelli, DB Rifkin
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1988
Pericellular proteolysis by neutrophils in the presence of proteinase inhibitors: effects of substrate opsonization
EJ Campbell, MA Campbell
The Journal of Cell Biology 1988
Superoxide-induced deimination of arginine in hematopoietic cells
PP Kamoun, E Schneider, M Dy
FEBS Letters 1988
Release of fibronectin fragments from endothelial cell monolayers exposed to activated leukocytes: Relationship to plasma fibronectin levels after particle infusion
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
Annals of the rheumatic diseases 1988
Conditioned medium from stimulated mononuclear leucocytes potentiates the ability of human neutrophils to damage human articular cartilage.
Bates EJ, Kowanko IC, Ferrante A
Annals of the rheumatic diseases 1988
Alpha-1-antitrypsin and the pathogenesis of emphysema
RA Stockley
Lung 1987
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

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