Structure and Function of C3a Anaphylatoxin*

  • T. E. Hugli
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 153)


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


Mast Cell Complement Activation Human Platelet Leukocyte Inhibition Factor Lower Molecular Weight Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • T. E. Hugli
    • 1
  1. 1.Department of ImmunologyResearch Institute of Scripps ClinicLa JollaUSA

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