Informace o publikaci
Histamin and its H4 receptor agonists decrease the reactive oxygen species production in human leukocytes and act as chemoattractants
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| Rok publikování | 2013 |
| Druh | Konferenční abstrakty |
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| Popis | Histamine, an endogenous biogenic amine, is an important chemical messenger which has numerous physiological roles in central and peripheral tissues [1,2]. These effects are mediated through four histamine receptors (H1R, H2R, H3R and H4R) which belong to the superfamily of G protein-coupled receptors [3]. We investigated the effects of histamine and the H4R agonists 4-methylhistamine and VUF8430 on the production of reactive oxygen species (ROS) and chemotaxis in human whole blood and isolated leukocytes. The antioxidant properties of histamine receptor agonists were investigated using total peroxyl radical-trapping antioxidant parameter analysis, oxygen radical absorbance capacity assay and NO-scavenging determination. 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 H4R agonist treatment (10-8-10-4 M) was tested by luminol-enhanced chemiluminescence, spontaneous or activated by opsonised zymosan particles (OZP) or phorbol-myristate-acetate (PMA). Further, Dimaprit (H2R agonist), Ranitidine (H2R antagonist) and JNJ10191584 (H4R antagonist) were used for confirmation of histamine effects mediated through different types of histamine receptors. Confocal microscopy was used for chemotactic measurements. None of the studied compounds had any antioxidant activity against ROS. H4R 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. Generally, the effects of all three compounds were similar but less profound in isolated leukocytes. Ranitidine more than JNJ10191594 averted the inhibition of ROS production by histamine or his agonists. H4R agonists had a positive chemotactic effect on the isolated leukocytes, but not directly on neutrophils. 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. Acknowledgements Supported by grant LD11010 of the Ministry of Education, Youth and Sports of the Czech Republic and by COST BM0806 Action. |