Immunologie tachyphylaxis, a mechanism of cellular protection from complement, perform and bacterial exotoxins

Nucleated cells treated with lytic doses of complement membrane attack complex (MAC), perform or streptolysin 0 (SLO) undergo a rapid process of necrotic cell death. We have described a 'complement-induced protection' phenomenon expressed by nucleated cells subjected to treatment with sublytic doses of MAC which become transiently protected from lytic doses of MAC within 30-50 minutes . More recent results obtained with murine perform and SLO have indicated that the phenomenon of induced-protection actually applies to a family of pore-forming proteins which similary introduce lesions in biological membranes and induce calcium influx. Moreover, it appears that such pore-formers induce cross-protection from lysis. Thus, treatment of K562 human erythroleukemia cells with sublytic doses of MAC induces in them protection from perforin, sublytic perforin protects from MAC and sublytic SLO protects from MAC and perforin. The general phenomenon has been termed 'Immunologie tachyphylaxis' to indicate the capacity of nucleated cells to develop resistance to immune attack following a brief exposure to sublytic doses of the cytolytic pore-formers of the immune system or related proteins. Treatment of K562 cells with the calcium ionophores A23187 or ionomycin, at sublytic doses, also conferred on them resistance to MAC and perforin. Cycloheximide and actinomycin D abrogated the protective activities of sublytic ionophores and MAC. These results indicate that calcium influx and protein synthesis are essential for development of immunologie tachyphylaxis.