Human platelet activation by C3a and C3a des-arg.
C3a liberated from C3 by treatment with C3 convertase (or by trypsin) induced aggregation of gel-filtered human platelets and stimulated serotonin release. At concentrations of 10(-10) M to 8 X 10(-12) M, C3a induced aggregation when added alone to platelets. However, at lower concentrations (2 X 10(-12) M) C3a did not aggregate platelets directly but exhibited highly significant synergism (two-way analysis of variance P less than 0.0001) with ADP in mediating platelet aggregation and release of serotonin. Removal of the C-terminus arginine from C3a abolished anaphylotoxin activity but did not affect the platelet-stimulating activity of the peptide. C3a and C3a des-arg were equally reactive in mediating platelet aggregation and release of serotonin. Further C3a and C3a des-arg exhibited synergism with ADP of equal significance in both aggregation and the release reaction. The concentrations of C3a required for the platelet-stimulating activity involve relatively small number of molecules per platelet (4,000-10,000 for the synergistic reaction with ADP). These data suggest the possibility of a C3a (C3a des-arg) receptor on human platelets. This premise is strengthened by the demonstration ultrastructurally of C3a on the platelet membrane subsequent to C3a stimulation.
D000244:Adenosine Diphosphate / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D043424:Carboxypeptidase B; D002268:Carboxypeptidases / Q000494:pharmacology; D002462:Cell Membrane / Q000648:ultrastructure; D002850:Chromatography, Gel; D003176:Complement C3 / Q000502:physiology*; D015926:Complement C3a; D003182:Complement C5 / Q000031:analogs & derivatives* / Q000502:physiology; D015937:Complement C5a, des-Arginine; D004357:Drug Synergism; D006801:Humans; D010974:Platelet Aggregation; D012701:Serotonin / Q000097:blood; D013917:Thrombin / Q000494:pharmacology
D003176:Complement C3; D003182:Complement C5; D015937:Complement C5a, des-Arginine; D012701:Serotonin; D000244:Adenosine Diphosphate; D015926:Complement C3a; D002268:Carboxypeptidases; D043424:Carboxypeptidase B; D013917:Thrombin