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Histamine suppresses in vitro synthesis of precursor (pro-C5) of the fifth complement component (C5) by mouse
Abstract:
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).
Insights
Histamine suppresses the synthesis of complement component C5 in mouse macrophages. This inhibition, mediated by histamine H2 receptors, affects both C5 protein production and its functional activity.
Area of Science:
- Immunology
- Pharmacology
Background:
- Complement component C5 (C5) plays a crucial role in the immune system.
- Macrophages are key immune cells involved in C5 production.
- Histamine is a biogenic amine with diverse physiological roles.
Purpose of the Study:
- To investigate the effect of histamine on C5 synthesis and function in mouse macrophages.
- To determine the specific histamine receptor involved in this interaction.
Main Methods:
- Primary mouse peritoneal macrophages (resident and thioglycollate-stimulated) were cultured in the presence of varying concentrations of histamine.
- C5 synthesis was assessed by measuring intracellular and secreted C5 antigen levels.
- C5 functional activity was determined by hemolytic assays.
- Histamine receptor involvement was explored using specific agonists and antagonists (cimetidine).
Main Results:
- Histamine significantly suppressed both functional and antigenic C5 synthesis in a dose-dependent manner.
- Maximal suppression was observed at 10(-3) M histamine.
- The inhibitory effects were mediated through histamine H2 receptors, as confirmed by experiments with agonists and the H2 antagonist cimetidine.
- Suppression of pro-C5 synthesis was identified as the primary mechanism.
Conclusions:
- Histamine, via H2 receptors, inhibits the synthesis and function of complement component C5 in mouse macrophages.
- This finding suggests a novel immunomodulatory role for histamine impacting the complement system.