Modulation of melittin-induced hemolysis of red blood cells

Various chemical agents with respect to their action on melittin-induced hemolysis can be subdivided into three main groups: neutral substances, inhibitors, and activators of hemolysis. Inhibitors-which include the divalent cations Ca2+ and Zn2+, albumin, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), and some other agents-inhibit melittin-induced hemolysis of erythrocytes; their blocking ability is significantly increased when the agents act on the early stages of peptide-membrane interaction. Melittin causes hemolysis at a rate that depends on time of preliminary incubation of the cells in physiological saline, irrespective of the presence or absence of inhibitors and activators. The rate of hemolysis increases with increasing preincubation time. These effects may be due to the existence of melittin-specific membrane inhibitory components (MICs) which initially protect the cell against the lytic action of peptides, but are probably desorbed from the membrane surface during cell dilution and incubation in physiological saline. A model of melittin-induced hemolysis is proposed according to which the features of hemolysis are determined by consecutive stages of peptide-membrane interactions and depend on whether or not an anti-lytic triple complex, including a membrane inhibitory component, an inhibitor, and the peptide is formed.