Activation of the complement attack mechanism in the fluid phase and its control by C567-INH: lysis of normal erythrocytes initiated by zymosan, endotoxin, and immune complexes.
Addition of zymosan-serum complexes to guinea pig erythrocytes in guinea pig complement-EDTA was found to result in substantial lysis of the bystander cells in the presence of polycations such as poly-L-lysine of 178,000 daltons. Involvement of the alternative C pathway was shown, and the optimum time, temperature, and eruthrocyte and polycation concentrations were defined; a surprising efficiency was observed at low temperature and high cell concentrations. Several lines of evidence indicated that this hemolysis was mediated via the C567 complex of the C system and modulated by serum inhibitors of C567 (C567-INH): lysis was observed only with zymosan-serum complexes possessing C-consuming activity; it was not observed in C5-depleted guinea pig serum but was restored upon addition of purified C5; the addition of partially purified C567-INH insubstantially depressed hemolysis; and poly-L-lysine which is known to neutralize C567-INH in solution resulted in substantial enhancement of hemolysis. We also sought to determine whether the addition of complement activators directly to erythrocyte-serum mixtures could result in the hemolysis of bystander erythrocytes. It was found that zymosan, endotoxin, antigen-antibody complexes, and aggregated human gamma-globulin each could initiate such bystander lysis under appropriate conditions. Lysis again was favored by increased erythrocyte concentrations, low temperatures, and the presence of polycations such as poly-L-lysine, and was found to be mediated via the C system. C567-INH blocked cytolysis whereas poly-L-lysine potentiated hemolysis by neutralization of C567-INH. These experiments emphasize the propensity for C567 formation and lysis of bystander erythrocytes during C activation generally, the role of C567-INH in the control of this lysis, and the susceptibility of these interactions to modulation by highly charged macromolecules.
D000818:Animals; D000936:Antigen-Antibody Complex; D003182:Complement C5 / Q000037:antagonists & inhibitors; D003183:Complement C6 / Q000037:antagonists & inhibitors; D003184:Complement C7 / Q000037:antagonists & inhibitors; D003165:Complement System Proteins / Q000276:immunology*; D004731:Endotoxins / Q000494:pharmacology*; D004912:Erythrocytes; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects*; D007074:Immunoglobulin G; D011107:Polylysine / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology*
D000936:Antigen-Antibody Complex; D003182:Complement C5; D003183:Complement C6; D003184:Complement C7; D004731:Endotoxins; D007074:Immunoglobulin G; D011107:Polylysine; D003165:Complement System Proteins; D015054:Zymosan