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Asbestos‐induced injury to cultured human pulmonary epithelial‐like cells: role of neutrophil elastase
Author(s) -
Kamp David W.,
Dunne Moyra,
Dykewicz Mark S.,
Sbalchiero Jane S.,
Weitzman Sigmund A.,
Dunn Marc M.
Publication year - 1993
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.54.1.73
Subject(s) - elastase , pancreatic elastase , proteases , cathepsin g , proteinase 3 , zymosan , asbestos , chrysotile , microbiology and biotechnology , biology , neutrophil elastase , immunology , in vitro , chemistry , biochemistry , myeloperoxidase , inflammation , enzyme , materials science , metallurgy
Abstract The mechanisms responsible for asbestos‐ induced pulmonary epithelial cell cytotoxicity, especially oxidant‐independent mechanisms, are not established. We determined whether human polymorphonuclear leukocyte (PMN) proteases contribute to asbestos‐induced damage to human pulmonary epithelial‐like cells (PECs) assessed using an in vitro chromium‐51 release assay. Serine antiproteases, phenylmethylsulfonyl fluoride and αι ‐antitrypsin, each ameliorated PEC injury induced by amosite asbestos and PMNs. A role for a specific proteinase, human neutrophil elastase (HNE), is supported by the facts that (1) asbestos increased HNE release assessed by an enzyme‐linked immunosorbent assay technique (1.7 ± 0.5 vs. 2.8 ± 0.5 μg/ml; P < .025), (2) purified HNE or porcine pancreatic elastase (PPE) each alone caused PEC detachment, (3) asbestos plus either HNE or PPE caused PEC lysis similar to that mediated by asbestos and PMNs, and (4) cationic agents released from PMNs were unlikely to be involved because polyanions did not ameliorate injury resulting from asbestos and PMNs. Compared to elastase, cathepsin G caused less PEC detachment and negligible augmentation in asbestos‐ induced PEC lysis. Asbestos increased the association of 125I‐labeled elastase with PECs nearly 50‐fold compared with PPE alone (14.4% vs. 0.3%, respectively; P < .01) and nearly 10‐fold compared with another particle, opsonized zymosan. We conclude that PMN‐derived proteases, especially elastase, may contribute to asbestos‐ induced lung damage by augmenting pulmonary epithelial cell injury.