Crocidolite Induces Prostaglandin I2 Release Mediated by Vitronectin Receptor and Cyclooxygenase-2 in Lung Cells

Abstract

Interstitial lung disease (ILD) produces disruption of alveolar walls with loss of functionality and scar tissue accumulation. Asbestosis is the ILD produced by the inhalation of asbestos fibers. This study attempts to elucidate the role of lung epithelial cells in the generation of asbestos-induced ILD. When exposed to crocidolite LA-4 cells had a decrease in viability and an increase in the release of lactate dehydrogenase (LDH) and 6-keto PGF(1alpha), a PGI(2) metabolite. PGI(2) release was mediated by cyclooxygenase-2 (COX-2) and vitronectin receptor (VNR). When LA-4 cells were treated with VNR inhibitors, either RGD (Arg-Gly-Asp) peptide or VNR blocking antibody, a statistically significant decrease in PGI(2) metabolite production was observed, but crocidolite-induced cytotoxicity was not prevented. These findings propose that crocidolite is coated by an RGD protein and binds VNR-inducing COX-2 expression and PGI(2) release. Moreover, when LA-4 cells were exposed to crocidolite in the presence of reduced serum culture media, PGI(2) production was prevented, and when bronchoalveolar lavage fluid (BALF) was added, PGI(2) production was rescued. Cytotoxicity did not occur, either in reduced serum culture media or when BALF was added. In conclusion, crocidolite requires the presence of an RGD protein coating the fibers to induce inflammation (PGI(2) production) and crocidolite alone cannot induce cytotoxicity in lung cells.