Role of reactive oxygen metabolites in crocidolite asbestos toxicity to mouse macrophages.

Crocidolite asbestos is toxic to macrophages in vitro. We hypothesize that this toxicity is mediated by the generation of reactive oxygen metabolites. Elicited mouse peritoneal macrophages were found to release reactive oxygen metabolites upon incubation with crocidolite asbestos in vitro. Crocidolite toxicity to both primary cultures of mouse peritoneal macrophages and P388D1 cells, a mouse macrophage-like cell line, could be prevented by a hypoxic environment or by addition of the reactive oxygen metabolite scavengers, superoxide dismutase and catalase. In addition, if crocidolite fibers were presoaked with the iron chelator deferoxamine, no macrophage death occurred. In an attempt to mimic crocidolite-induced cytotoxicity, P388D1 cells or primary elicited macrophages were exposed to the nontoxic mineral particle titanium dioxide in the presence and absence of ferric chloride. Titanium dioxide was only lethal when ferric chloride was added. This toxicity was prevented by superoxide dismutase, catalase, or deferoxamine. These results suggest that crocidolite-induced injury to macrophages depends on the formation of reactive oxygen metabolites. Iron present in crocidolite fibers may catalyze the production of hydroxyl radical from superoxide anion and hydrogen peroxide generated during phagocytosis. These highly reactive hydroxyl radicals are postulated to mediate lethal cell injury.