title: Role of the N-terminal regions of hog C3a, C5a and C5a-desArg in their biological activities.
abstract: The N-terminal regions of the complement peptides C3a, C5a and C5a-desArg (purified from yeast-activated hog serum) were gradually shortened by incubation with leucine amino peptidase. This treatment led to the following changes in the biological activities of these peptides: the potencies of C5a and C5a-desArg in aggregation of human polymorphonuclear leukocytes and of guinea-pig platelets, and their ability to deactivate these cells were gradually diminished; the chemotactic effect of C5a-desArg on human leukocytes was similarly lowered, while the chemotactic potency of C5a was even increased up to the loss of the first 12 N-terminal amino acids. However, after removal of the whole N-terminal region (i.e. 20 amino acids distal of the first disulfide bridge) the potency of both peptides was decreased to a few percent. In contrast, C3a totally lost its platelet-aggregating as well as deactivating activity already after cleavage of 10-15 N-terminal amino acids by LAP. On leukocytes, on the other hand, C3a retained some activity even after the loss of the whole N-terminal region. These results indicate that the N-terminal regions play an important role for biological activities of the three complement peptides, possibly by stabilizing the optimal conformation of their C-terminal regions which contain the receptor-activating domains.
mesh_terms: D000818:Animals; D002449:Cell Aggregation; D002465:Cell Movement; D003176:Complement C3 / Q000276:immunology*; D015926:Complement C3a; D003182:Complement C5 / Q000031:analogs & derivatives* / Q000276:immunology*; D015936:Complement C5a; D015937:Complement C5a, des-Arginine; D066298:In Vitro Techniques; D007931:Leucyl Aminopeptidase / Q000494:pharmacology; D007962:Leukocytes / Q000276:immunology; D010974:Platelet Aggregation; D013552:Swine
chemical_list: D003176:Complement C3; D003182:Complement C5; D015937:Complement C5a, des-Arginine; D015926:Complement C3a; D015936:Complement C5a; D007931:Leucyl Aminopeptidase