Crocidolite induces prostaglandin I(2) release mediated by vitronectin receptor and cyclooxygenase-2 in lung cells.
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.
Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20824, USA. fleyva1@jhmi.edu
Francisco J
FJ
Leyva
Kevan
K
Roberts
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D011464:Epoprostenol / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects
D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D017638:Asbestos, Crocidolite; D015121:6-Ketoprostaglandin F1 alpha; C047981:arginyl-glycyl-aspartic acid; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2