Cutaneous responses to human C 3 anaphylatoxin in man.

Intracutaneous injection of the low molecular weight fragment (C3a) of the third component of human complement caused pruritus, wheal and axon-reflex erythema in human skin. The response was maximal at 5–10 min after injection and dose-dependent between 15 and 600 ng. On a molar basis, C3a was more effective than histamine. The response to C3 anaphylatoxin required the release of 10 to 15 moles of histamine per mole of C3a. Biopsies of skin revealed mast cell degranulation and free metachromatic granules in sites injected with 320 or 2000 ng C3a. Margination and extravascular emigration of neutrophilic granulocytes was observed about cutaneous vessels within 10 min following injection of 2 μg of the polypeptide. The wheal and erythema were diminished by prior injection of antihistamine agents; axon-reflex erythema was selectively abolished by local anaesthesia. After brief incubation of C3a with the serum exopeptidase, anaphylatoxin inactivator, the wheal and flare were decreased by greater than 95% and granulocyte accumulation was prevented.