Publication details
Histamin and its H2/H4 receptor agonists decrease the reactive oxygen species production in human leukocytes and may act as a chemoattractant
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| Year of publication | 2013 |
| Type | Conference abstract |
| Citation | |
| Description | Background: Histamine, an endogenous biogenic amine, is an important chemical messenger which has numerous physiological roles in central and peripheral tissues. These effects are mediated through four histamine receptors (H1R, H2R, H3R and H4R). We investigated the effects of histamine and the H2R/H4R agonists (dimaprit, 4-methylhistamine, VUF8430) on the production of reactive oxygen species (ROS) and chemotaxis in human whole blood leukocytes. Methods: The antioxidant properties of tested compounds were measured using several methods (TRAP; ORAC; luminol-HRP-H2O2; NO scavenging). ATP activity was used for evaluation of cell viability. The ability of isolated leukocytes or leukocytes in the whole blood of healthy human volunteers to produce ROS after histamine or H2R/H4R agonist treatment was tested by luminol-enhanced chemiluminescence, spontaneous or activated by opsonised zymosan particles (OZP) or phorbol-myristate-acetate (PMA). Confocal microscope was used for chemotactic measurement. Results: None of the studied compounds had any antioxidant activity against ROS. H4R and H2R agonists significantly decreased the spontaneous and OZP-activated chemiluminescence response in whole blood leukocytes in a dose-dependent manner. In contrast, only VUF8430 was dose-dependently effective when whole blood leukocytes were activated with PMA. Ranitidine (H2R antagonist), more than JNJ10191594 (H4R antagonist) prevented the effect of histamine or its agonists. H4R agonists had a positive chemotactic effect on the isolated leukocytes, but not on neutrophils directly. Conclusions: It can be concluded that the inhibition of ROS production by the tested compounds was caused by H2R rather than by H4R activation. The specificity of the H4R agonists tested is dependent on the concentration used and, especially at high concentrations, the signal may be transduced mainly through H2R. We assume from our results that neutrophils do not express active H4R. Supported by grant LD11010 of the Ministry of Education, Youth and Sports of the Czech Republic and by COST BM0806 Action. |