Differential Effects of the Complement Peptides, C5a and C5a des Arg

The ability of purified anaphylatoxins to induce human lung mast cell mediator release was investigated. In eight anti-IgE responsive (histamine release = 22±5%, mean±SEM) mast cell preparations of 1-96 % purity, C5a and C5a des Arg (0.55 pg/ml to 55 pg/ml), failed to elicit or potentiate histamine release; lung fragments were similarly unresponsive. The re-lated peptide C3a was also inactive. All anaphylatoxins failed to induce mast cell leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) release. LTC4 release was also negligible from baso-phils where C5a was a potent histamine release stimulus. Su-pernatants from C5a-challenged mast cells remained fully ac-tive on basophils, excluding carboxypeptidase inactivation of C5a as an explanation for the lung mast cell results. In contrast to lung, skin mast cells were C5a-responsive (histamine release = 8±1%, at 55 gsg/ml, n = 2). We conclude that C5a, though devoid of activity on the human lung mast cell, is a human basophil and skin mast cell secretogogue. These findings dem-onstrate significant organ-specific heterogeneity in mast cell responsiveness