Complement activation and attack on autologous cell membranes induced by streptolysin-O.
Streptolysin-O damages mammalian membranes through generation of large transmembrane channels formed by membrane-inserted polymers of the toxin (S. Bhakdi et al., Infect. Immun. 47:52-60, 1985). We here report that the native toxin binds naturally occurring human serum immunoglobulin G antibodies to form immune complexes with potent complement-activating capacity. Nanomolar concentrations of toxin added to antibody-containing serum cause rapid consumption of C4 and C5 hemolytic activity and 30 to 90% C3 conversion within 10 to 60 min at 37 degrees C. After binding to target membranes, streptolysin-O polymers serve as foci for antibody-dependent complement activation, which proceeds to completion with the formation of terminal C5b-9 complexes on the autologous cells. The binding and insertion of a primarily water-soluble bacterial product into a host cell membrane has thus been shown to generate a stable and hyperactive focus for activation of and self-attack by the complement system. We suggest that this process perpetuates local tissue damage, deviates host complement action away from the invading bacteria, and may possibly play a role in the pathogenesis of poststreptococcal disease.
D000936:Antigen-Antibody Complex / Q000276:immunology; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000633:toxicity; D002462:Cell Membrane / Q000187:drug effects; D003167:Complement Activation / Q000187:drug effects*; D004910:Erythrocyte Membrane / Q000187:drug effects; D006460:Hemolysin Proteins; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D013301:Streptolysins / Q000276:immunology / Q000633:toxicity*
D000936:Antigen-Antibody Complex; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D007074:Immunoglobulin G; D013301:Streptolysins; C021091:staphylococcal alpha-toxin; C025964:streptolysin O