Direct effects of neutrophil oxidants on elastase-induced extracellular matrix proteolysis

Stephen E McGowan; Joel J Murray

doi:10.1164/arrd.1987.135.6.1286

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Journal article

Direct effects of neutrophil oxidants on elastase-induced extracellular matrix proteolysis

Stephen E McGowan and Joel J Murray

The American review of respiratory disease, Vol.135(6), pp.1286-1293

06/1987

DOI: 10.1164/arrd.1987.135.6.1286

PMID: 3035975

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Abstract

Oxidant species produced by human polymorphonuclear leukocytes (PMN) inactivate alpha-1-protease inhibitor and thus may indirectly enhance neutrophil elastase-induced proteolysis. It is unclear, however, if PMN-derived oxidants directly enhance proteolysis of extracellular matrix by neutrophil elastase. Matrix was produced by neonatal rat aortic smooth muscle cells and pulse-labeled with 3H-lysine to allow identification of the collagen-specific amino acid, hydroxylysine (3H-HL), and the elastin specific amino acid, desmosine (3H-DES). The smooth muscle cells were lysed, and the remaining matrix was used as a culture surface and a proteolytic substrate for intact PMN and purified neutrophil elastase. Proteolysis of collagen and elastin were quantified by chromatographic separation of the marker amino acids 3H-HL and 3H-DES, which were released into the supernatant or remained in the matrix after a 3-h incubation at 37 degrees C. The peptide, formyl-methionine-leucine-phenylalanine (FMLP), produced more rapid release of myeloperoxidase than did phorbol myristate acetate (PMA), which produced more release of O2- and H2O2 than did FMLP. The percent release of total matrix 3H-DES in the presence of PMN + FMLP was 2.45 +/- 0.19% (mean +/- SE, n = 6) and with PMN + PMA it was 1.32 +/- 0.1% (n = 6, p less than 0.01). The release of matrix 3H-HL did not differ. Neutrophil cytoplasts, which produced O-2 and H2O2 but lacked azurophilic granules, did not significantly enhance either elastin or collagen degradation by purified neutrophil elastase (NE).

Peroxidase - pharmacology

Elastin - metabolism

Neutrophils - enzymology

Oxygen - physiology

Humans

Rats

Pancreatic Elastase - metabolism

Blood Proteins - metabolism

Rats, Inbred Strains

alpha 1-Antitrypsin

Cell Adhesion

Extracellular Matrix - enzymology

Hydrolysis

Collagen - metabolism

Animals

Hydrogen Peroxide - physiology

Cytoplasmic Granules - metabolism

Superoxides - metabolism

Peptide Hydrolases - metabolism

Details

Title: Subtitle: Direct effects of neutrophil oxidants on elastase-induced extracellular matrix proteolysis
Creators: Stephen E McGowan
Joel J Murray
Resource Type: Journal article
Publication Details: The American review of respiratory disease, Vol.135(6), pp.1286-1293
Publisher: United States
DOI: 10.1164/arrd.1987.135.6.1286
PMID: 3035975
ISSN: 0003-0805
eISSN: 2376-3752
Language: English
Date published: 06/1987
Academic Unit: International Programs; Internal Medicine
Record Identifier: 9983983653902771

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