Anaphylatoxin C3a enhances mucous glycoprotein release from human airways in vitro.

Abstract

Because complement component C3a anaphylatoxin may be generated during the course of pulmonary inflammatory reactions, the ability of C3a to affect mucous glycoprotein (MGP) secretion from cultured human airways was investigated. C3a, but not C3a des Arg, caused a dose-related increase in MGP release (maximal after 4-6 h), with as little as 15 .mu.g of C3a/ml stimulating a 40% increase. The experimental evidence suggested that immunologically specific C3a was required for the secretagogue actions, as monospecific anti-C3a inhibited the reaction, as well as specifically absorbing the secretagogue from solution. It appeared that C3a does not require mast cells activation, eicosanoid generation or macrophage-derived mucus secretagogue synthesis for its effects: no evidence of histamine release accompanied C3a-induced MGP release, and dibutyryl cAMP failed to affect C3a-induced MGP release, while reducing the actions of reversed anaphylaxis; MGP release caused by C3a was not influenced by eicosatetraynoic acid or specific cyclooxygenase inhibitors, and no leukotrienes were detectable on the supernatants of C3a-stimulated airways; and cycloheximide failed to affect C3a secretion-stimulating actions. Thus, C3a is a potent mucus secretagogue, and possibly, acts directly as a glandular stimulant. C3a generated in the course of pulmonary inflammation might contribute to the mucus secretion associated with pulmonary infections.