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The effects of histamine and serotonin on polymorphonuclear leukocyte accumulation in the rat
Abstract:
Histamine and serotonin were evaluated for their effects on rat polymorphonuclear leukocyte (PMN) accumulation in vivo and PMN migration in vitro. Both of the mediators inhibited the accumulation of PMNs when injected into the pleural cavity in a saline vehicle, and reduced the PMN content of the peripheral blood. Histamine also reduced the cellular influx when administered in combination with an intrapleural injection of carrageenan. Peripheral blood leukocytes removed from rats injected intrapleurally with histamine and carrageenan had a lesser chemotactic responsiveness compared with those removed from rats injected only with carrageenan. The effects of histamine in reducing PMN accumulation was abolished by treatment with cimetidine, an H2 antagonist, but not by treatment with chlorpheniramine, an H1 antagonist. These results suggest that a local release of histamine may play a role in reducing cellular infiltration into an inflammatory site.
Insights
Histamine and serotonin reduce polymorphonuclear leukocyte (PMN) accumulation during inflammation. Histamine
Area of Science:
- Immunology and Pharmacology
Background:
- Inflammation involves the accumulation of polymorphonuclear leukocytes (PMNs) at the affected site.
- The roles of endogenous mediators like histamine and serotonin in modulating inflammatory cell infiltration are not fully understood.
Purpose of the Study:
- To investigate the effects of histamine and serotonin on rat PMN accumulation in vivo and migration in vitro.
- To determine the specific histamine receptor subtype involved in modulating PMN accumulation.
Main Methods:
- In vivo studies involved intrapleural injections of histamine and serotonin in rats to assess PMN accumulation.
- In vitro studies evaluated PMN migration.
- Chemotactic responsiveness of peripheral blood leukocytes was assessed after histamine and carrageenan administration.
- Pharmacological blockade using H1 (chlorpheniramine) and H2 (cimetidine) antagonists was employed.
Main Results:
- Both histamine and serotonin inhibited PMN accumulation in the pleural cavity and reduced peripheral blood PMN counts.
- Histamine reduced cellular influx even when combined with carrageenan-induced inflammation.
- Leukocytes from rats treated with histamine and carrageenan showed reduced chemotactic responsiveness.
- The inhibitory effect of histamine on PMN accumulation was mediated via H2 receptors, as it was blocked by cimetidine but not chlorpheniramine.
Conclusions:
- Histamine and serotonin act as negative regulators of PMN infiltration into inflammatory sites.
- Histamine's inhibitory effect on PMN accumulation is primarily mediated through H2 receptor activation.
- These findings suggest that local histamine release may play a protective role in limiting excessive cellular infiltration during inflammation.