Intracellular calcium antagonist protects cultured peritoneal macrophages against anthrax lethal toxin-induced cytotoxicity

The lethal toxin of Bacillus anthracis is central to the pathogenesis of an thrax. Using primary cultures of mouse peritoneal macrophages, we have demo nstrated that intracellular calcium release inhibitors protect against anth rax lethal toxin-induced cytotoxicity. The cytolytic effect of anthrax leth al toxin was markedly reduced by dantrolene, an inhibitor of calcium releas e from intracellular calcium stores. Pretreatment of macrophages with cyclo sporin A, which has been shown to be a potent inhibitor of calcium release from mitochondria, also protected cells against cytotoxicity. These results indicate that calcium release from intracellular store may be an essential step for the propagation of anthrax lethal toxin-induced cell damage in ma crophages. Thus our findings suggest that dantrolene, cyclosporin A, and po ssibly other drugs affecting intracellular calcium pools might be effective ly preventing the toxicity from anthrax lethal toxin.