CLOSTRIDIAL GAS-GANGRENE - EVIDENCE THAT ALPHA-TOXIN AND THETA-TOXIN DIFFERENTIALLY MODULATE THE IMMUNE-RESPONSE AND INDUCE ACUTE TISSUE NECROSIS

The rapid extension of necrosis and an absence of polymorphonuclear le ukocytes (PMNL) at the site of infection are two hallmarks of Clostrid ium perfringens gas gangrene, While both cu and a toxins profoundly af fect PMNL function and viability in vitro, their roles in muscle destr uction and impairment of the inflammatory response in vivo have not be en investigated, Comparative histopathologic examinations were perform ed on animals infected with either wild-type C. perfringens, or isogen ic, toxin-deficient mutants of C. perfringens, Tissue destruction was modest in animals infected with the alpha toxin-deficient mutant; dest ruction was more pronounced in tissues infected with the theta toxin-d eficient mutant or the wild-type strain. alpha and theta toxins also d isplayed differing abilities to modulate the inflammatory response, Hi stopathologic studies in which recombinant toxins were injected togeth er with killed, washed C. perfringens further substantiated these tiss ue-destructive and differential antiinflammatory effects.