Structure and Function of C3a Anaphylatoxin*

摘要: The C3a molecule is one of three activation fragments from the complement cascade, a family factors that include C3a, C4a, and C5a. Early recognition more than bio active fragment was generated during cascade must be credited to COCHRANE MULLER-EBERHARD (1968) DIAS DA SILVA et al. (1967). These investigators were first use purified components human demonstrate, then characterize, C3. In previous studies activated in serum, bioassays used detected only factor C5a (actually C5adesArg). realized, even using C1 esterase, C4, C2, C3, anaphylatoxin released C3 not stablized unless digest acidified pH 2-5, according earlier observations STEGEMANN (1964). Later work by BOKISCH MuLLER-EBERHARD (1970) would explain why acid treatment successful. Acidification presumably prevented residual carboxypeptidase (serum carboxypeptide N) isolates removing an essential C-terminal arginine inactivating newly formed anaphylatoxin. It this lability bioactivity serum had its discovery prior isolation components. went on separate principal larger protein reconstituted C3—C3 convertase system gel filtration. They demonstrated lower molecular weight factor: (a) induced smooth-muscle contraction tachyphylactic itself but cross-tachyphylactic C5-derived anaphylatoxin; (b) enhanced vascular permeability when injected into skin; (c) degranulated guinea pig ileal mast cells; (d) promoted histamine release rat peritoneal cells. SILVA’S group originally termed F(a)C3, i.e., third component complement. identified as anaphylatoxin, assuming it analog “classical” We will refer here primarily because biologic action anaphylactoid nature, functionally inaccurate designation. However, recognized nomenclature common usage still refers collectively anaphylatoxins.