Iron mobilization from crocidolite as enhancer of collagen content in rat lung fibroblasts.
Asbestos exposure causes pulmonary fibrosis by mechanisms that remain uncertain. There is increasing evidence that iron from asbestos is responsible for many of its effects. In this paper, we investigated the effect of iron mobilized from crocidolite asbestos on collagen content in rat lung fibroblast cultures under serum-free conditions. Crocidolite (2, 4, 6 microg/cm2 well) increased collagen content in a dose-dependent manner (+42 +/- 8, +92 +/- 10, and +129 +/- 13% vs controls). This effect was specific for collagen, since it did not alter total protein content and was inhibited by the iron chelator deferoxamine (DFO). Preincubation of crocidolite with citrate (1 mM) for 48 hr resulted in iron mobilization (51 microM) and increased collagen production (>3-fold) 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 se 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 plays a role in collagen increase occurring during asbestosis.
Gardi
C
C
Institute of General Pathology, University of Siena, Italy.
Calzoni
P
P
Ferrali
M
M
Comporti
M
M
D000818:Animals; D017638:Asbestos, Crocidolite / Q000737:chemistry / Q000633:toxicity*; D001195:Asbestosis / Q000209:etiology / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004247:DNA / Q000032:analysis; D005347:Fibroblasts; D007501:Iron / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000032:analysis; D051381:Rats
D011506:Proteins; D017638:Asbestos, Crocidolite; D003094:Collagen; D004247:DNA; D007501:Iron