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 anthrax. Using primary cultures of mouse peritoneal macrophages, we have demonstrated that intracellular calcium release inhibitors protect against anthrax lethal toxin-induced cytotoxicity. The cytolytic effect of anthrax lethal toxin was markedly reduced by dantrolene, an inhibitor of calcium release from intracellular calcium stores. Pretreatment of macrophages with cyclosporin 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 macrophages. Thus our findings suggest that dantrolene, cyclosporin A, and possibly other drugs affecting intracellular calcium pools might be effectively preventing the toxicity from anthrax lethal toxin.
CBR Department, Agency for Defense Development, Yuseong, Taejon.
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Shin
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Hur
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Kim
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Park
Y M
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Park
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Lee
D000818:Animals; D000881:Anthrax / Q000188:drug therapy; D000935:Antifungal Agents / Q000494:pharmacology; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000633:toxicity*; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology*; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D014774:Virulence
D000935:Antifungal Agents; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D002614:Chelating Agents; D009125:Muscle Relaxants, Central; C030325:anthrax toxin; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D016572:Cyclosporine; D003620:Dantrolene; D002118:Calcium