Comparative study on biological activities of various anaphylatoxins (C4a, C3a, C5a). Investigations on their ability...

Several anaphylatoxic substances (human C3a, guinea pig C3a, human C4a, guinea pig C5a, and a synthetic C3a-related hexapeptide) were compared with regard to their ability to induce secretion of [3H] serotonin from guinea pig platelets. Functional identity of the C3a preparations, C4a, and the hexapeptide was demonstrated by the phenomenon of crossed desensitization. Whereas C3a of human and guinea pig origin proved to be qualitatively and quantitatively identical, C4a expressed only 3% of the activity of the C3 fragments on a molar basis. Investigations with goat anti-guinea pig C3a demonstrate that human and guinea pig C3a possess one antigenic determinant in common; however, this determinant is not the C-terminal amino acid sequence. Addition of the anaphylatoxins with low doses of thrombin led to a potentiation of [3H] serotonin release from the platelets. Under these conditions C3a concentrations of 1.5 X 10(-10) mumol/liter (65 pg of C3a) could be detected. Thus the platelet system represents the most sensitive in vitro assay known for evaluation of biological activity of the C3a anaphylatoxins.