Anaphylatoxin-induced neutrophil chemotaxis and aggregation. Limited aggregation and specific desensitization induced by human C3a and synthetic C3a octapeptides

Abstract

Human neutrophil aggregation was induced by highly purified human C3a and chemically synthetic COOH-terminal peptides of C3a (C3a-8R; Ala-Ala-Ala-Leu-Gly-Leu-Ala-Arg) in a dose-dependent manner and was 40% of human C5a-induced aggregation at each optimal concentration. In contrast to C5a and formyl-Met-Leu-Phe (f-MLP), C3a and C3a-8R showed little chemotactic activity. Specific desensitization of neutrophil aggregation was observed with C3a, C3a-8R, C5a and f-MLP, but not with C3a-des-Arg-7R, indicating that the human neutrophil has C3a-specific binding sites which are different from C5a and f-MLP receptors. An additive effect on aggregation was observed at suboptimal concentrations of C5a (1 X 10(-8) M) and C3a (1 X 10(-6) M) or C3a-8R (1 X 10(-5) M). These studies suggest that a subpopulation of human neutrophils have specific binding sites for C3a and C3a may work cooperatively with C5a during the process of neutrophil activation by increasing aggregation and lysosomal enzyme release.