Selective cytolysis by a protein toxin as a consequence of direct interaction with the lymphocyte plasma membrane

Two lines of evidence support the concept that cardiotoxin from Naja naja siamensis interacts directly with the plama membrane to produce selective cytolysis of lymphocytes. Toxin adsorbed to the wells of microtiter plates retained the ability to lyse murine T-lymphocytes, but lost the ability to destroy natural killer cells, whereas soluble toxin obliterated both cell types. Second, toxin covalently coupled to 100-μm-diameter agarose beads, such that endocytosis would be precluded, effectively lysed L1210 tumor T-lymphocytes. Although differences were observed among susceptibilities of a variety of mouse and human tumor lymphocyte cell lines to toxin-mediated lysis, these differences were not so great as the differences between tumor and normal lymphocytes. The intrinsic selectivity of the toxin for T-lymphocytes, plus its retention of cytolytic potential when affixed to a solid support, suggests that such a protein could be applied therapeutically. In addition, based upon activity which is temperature-independent and not influenced by the absence or presence of external calcium, it appears that the toxin's mode of action may be different from that involved with erythrocyte hemolysis or with skeletal or cardiac muscle depolarization.