Histamine suppresses in vitro synthesis of precursor (pro-C5) of the fifth complement component (C5) by mouse peritoneal macrophages.

Soluble histamine added to mouse peritoneal macrophages in culture suppressed the synthesis of the functional and antigenic complement component C5. Synthesis of intracellular C5 antigen by resident macrophages was suppressed by 16 to 80%, and functional C5 activity by 13.6 to 87.2% at concentrations of histamine ranging from 10(-6) M to 10(-3) M, respectively; secretion of C5 protein was depressed by 18.3 to 85.5% and hemolytic C5 by 8 to 80%. In thioglycollate-stimulated exudates, intracellular synthesis of C5 protein was reduced by 3.3 to 72.3% and functional C5 activity by 7.6 to 73.5% using similar concentrations of histamine; secreted C5 protein was inhibited by 8.9 to 75.7% and functional activity by 4 to 78%. The suppression of C5 activity in resident and thioglycollate-stimulated cultures was dependent on the dose of histamine with maximal suppression occurring at a concentration of 10(-3) M. Experiments in which specific histamine agonists were used confirmed that the action was mediated by the H2 receptor. The inhibition of C5 antigenic protein synthesis paralleled that detected for functional C5. Immunochemical analysis of C5 antigen synthesized under the influence of histamine indicated that suppression of synthesis of pro-C5 was the major mechanism responsible for the depression of C5 produced under these conditions. The inhibitory effects produced by histamine were shown to be mediated by histamine type 2 receptors as indicated by abrogation of the inhibition by cimetidine (H2 antagonist).