Factor C3f is a spasmogenic fragment released from C3b by factors I and H: the heptadeca-peptide C3f was synthesized and characterized.
C3f, a heptadeca-peptide having the amino acid sequence of NH2-Ser-Ser-Lys-Ile-Thr-His-Arg-Ile-His-Trp-Glu-Ser-Ala-Ser-Leu-Leu-Arg- COOH, is liberated during the catabolic degradation of C3b in serum. The amino acid sequence of C3f is known both from the cDNA-derived structure of C3 and from protein analysis after isolation of the natural factor. C3f was synthesized by solid phase peptide synthesis. Both natural and synthetic C3f had identical retention times by RP-18 high performance liquid chromatography (HPLC) analysis and the respective amino acid compositions agreed with the expected theoretical values. C3f, but not des-Arg-C3f, was weakly spasmogenic inducing contraction of guinea pig ileum at a level of 5-10 x 10(-6) M. Since C3f and C3a were cross-tachyphylactic, it was concluded that these two spasmogens compete for the same receptors. Both C3f and des-Arg-C3f at concns of 1-4 x 10(-4) M enhanced vascular permeability in guinea pig skin. These observations further suggest that C3f functionally resembles C3a anaphylatoxin. Formation of C3f in human serum following CVF activation of C3 could be demonstrated by radioimmunoassay (RIA). Digestion of C3f with purified human serum carboxypeptidase N produced C3f-desArg. These observations suggest that when serum complement protein C3 undergoes conversion to C3b, further degradation by Factors H and I readily generates C3f. C3f is a weak spasmogen that functions like C3a anaphylatoxin and C3f-desArg is a major metabolite in serum.
Ganu
V S
VS
Pharmaceuticals Division, CIBA-GEIGY Corporation, Summit, NJ 07901.
Müller-Eberhard
H J
HJ
Hugli
T E
TE
D000595:Amino Acid Sequence; D000818:Animals; D002199:Capillary Permeability; D002851:Chromatography, High Pressure Liquid; D003176:Complement C3 / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D003179:Complement C3b / Q000378:metabolism*; D003180:Complement C3b Inactivator Proteins / Q000494:pharmacology*; D017242:Complement Factor H; D017244:Complement Factor I; D004546:Elapid Venoms / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D011863:Radioimmunoassay; D012697:Serine Endopeptidases / Q000494:pharmacology*
C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D004546:Elapid Venoms; C016310:cobra venom factor; C046821:complement C3f; D003179:Complement C3b; D017242:Complement Factor H; D012697:Serine Endopeptidases; D017244:Complement Factor I