ASBESTOS-INDUCED INJURY TO CULTURED HUMAN PULMONARY EPITHELIAL-LIKE CELLS - ROLE OF NEUTROPHIL ELASTASE

The mechanisms responsible for asbestos-induced pulmonary epithelial c ell cytotoxicity, especially oxidant-independent mechanisms, are not e stablished. We determined whether human polymorphonuclear leukocyte (P MN) proteases contribute to asbestos-induced damage to human pulmonary epithelial-like cells (PECs) assessed using an in vitro chromium-51 r elease assay. Serine antiproteases, phenylmethylsulfonyl fluoride and alpha1-antitrypsin, each ameliorated PEC injury induced by amosite asb estos and PMNs. A role for a specific proteinase, human neutrophil ela stase (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 mug/ml; P < .025), (2) purified HNE or porc ine pancreatic elastase (PPE) each alone caused PEC detachment, (3) as bestos plus either HNE or PPE caused PEC lysis similar to that mediate d by asbestos and PMNs, and (4) cationic agents released from PMNs wer e unlikely to be involved because polyanions did not ameliorate injury resulting from asbestos and PMNs. Compared to elastase, cathepsin G c aused less PEC detachment and negligible augmentation in asbestos-indu ced PEC lysis. Asbestos increased the association of I-125-labeled ela stase with PECs nearly 50-fold compared with PPE alone (14.4% vs. 0.3% , respectively; P < .01) and nearly 10-fold compared with another part icle, opsonized zymosan. We conclude that PMN-derived proteases, espec ially elastase, may contribute to asbestos-induced lung damage by augm enting pulmonary epithelial cell injury.