Anaphylatoxin C3a enhances mucous glycoprotein release from human airways in vitro.
Because C3a may be generated during the course of pulmonary inflammatory reactions, we investigated the ability of C3a to affect mucous glycoprotein (MGP) secretion from cultured human airways. C3a, but not C3a des Arg, caused a dose-related increase in MGP release (maximal after 4-6 h), with as little as 15 micrograms of C3a per milliliter 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. Moreover, it appeared that C3a does not require mast cell activation, eicosanoid generation, or macrophage-derived mucus secretagogue synthesis for its effect, since (a) 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; (b) 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 (c) cycloheximide failed to affect C3a secretion-stimulating actions. Thus, C3a is a potent mucus secretagogue, and, possibly, acts directly as a glandular stimulant. It seems likely that C3a generated in the course of pulmonary inflammation might contribute to the mucus secretion associated with pulmonary infections.
Marom
Z
Z
Shelhamer
J
J
Berger
M
M
Frank
M
M
Kaliner
M
M
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000706:Anaphylatoxins / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D003176:Complement C3 / Q000276:immunology / Q000494:pharmacology*; D015926:Complement C3a; D006636:Histamine Release; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007163:Immunosorbent Techniques; D008264:Macrophages / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology; D009088:Mucoproteins / Q000378:metabolism*; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology*
D000706:Anaphylatoxins; D001095:Arachidonic Acids; D003176:Complement C3; D007106:Immune Sera; D009088:Mucoproteins; D010455:Peptides; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D015926:Complement C3a