Human C5a des Arg increases vascular permeability.
C5a were generated in human plasma by incubation with zymosan in the presence of a carboxypeptidase B inhibitor. The carboxypeptidase inhibitor was added to prevent cleavage of the carboxyl terminal arginine from C5a and enabled it to be purified on the basis of spasmogenic activity on the guinea-pig isolated ileum. When injected into rabbit skin, purified C5a induced marked plasma leakage over a 30-min period, but only if the substance was first mixed with a vasodilator substance such as prostaglandin (PG)E2. The responses to C5a + PGE2 did not appear to be related to anaphylatoxic, histamine-releasing activity because an antihistamine, mepyramine, had only a small effect on plasma leakage. Further, removal of the carboxyl terminal arginine by carboxypeptidase B abolished activity on the ileum but not in the skin. The observation that both human C5a and C5a des Arg were able to increase vascular permeability in vivo suggested a parallel with leukotactic activity in vitro. In support of this, no responses to C5a + PGE2 were obtained in rabbits depleted or circulating polymorphonuclear leukocytes. Thus, inflammatory edema resulting from extravascular complement activation may be dependent on 2 components: a leukocyte/endothelial cell interaction triggered by C5a, and the concomitant generation of a vasodilator, prostaglandin.
D000706:Anaphylatoxins; D000818:Animals; D002199:Capillary Permeability; D043424:Carboxypeptidase B; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D003167:Complement Activation; D003176:Complement C3; D015926:Complement C3a; D003182:Complement C5; D015936:Complement C5a; D005122:Exudates and Transudates / Q000276:immunology; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D009504:Neutrophils / Q000276:immunology; D010455:Peptides; D011458:Prostaglandins E / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011817:Rabbits
D000706:Anaphylatoxins; D003176:Complement C3; D003182:Complement C5; D010455:Peptides; D011458:Prostaglandins E; D015926:Complement C3a; D015936:Complement C5a; D002268:Carboxypeptidases; D043424:Carboxypeptidase B; D011738:Pyrilamine