IRON MOBILIZATION FROM CROCIDOLITE AS ENHANCER OF COLLAGEN CONTENT INRAT LUNG FIBROBLASTS

Asbestos exposure causes pulmonary fibrosis by mechanisms that remain uncertain. There is increasing evidence that iron from asbestos is res ponsible for many of its effects. In this paper, we investigated the e ffect of iron mobilized from crocidolite asbestos on collagen content in rat lung fibroblast cultures under serum-free conditions. Crocidoli te (2, 4, 6 mu g/cm(2) well) increased collagen content in a dose-depe ndent manner (+42 +/- 8, +92 +/- 10, and +129 +/- 13% vs controls). Th is effect was specific for collagen, since it did not alter total prot ein content and was inhibited by the iron chelator deferoxamine (DFO). Preincubation of crocidolite with titrate (1 mM) for 48 kr resulted i n iron mobiIization (51 mu M) and increased collagen production (> 3-f old) in treated cells. These effects occurred without the intervention of serum factors. The absence of cell damage, proliferation or lipid peroxidation leads to the supposition that iron from crocidolite per s e may act as a profibrogenic agent. Although the in vivo participation of other cells and factors cannot be excluded, we conclude that iron released from crocidolite Flays a role in collagen increase occurring during asbestosis. BIOCHEM PHARMACOL 53;11:1659-1665, 1997. (C) 1997 E lsevier Science Inc.