Differing regulation of major histocompatibility class II and adhesion molecules on human umbilical vein endothelial cells by serotonin.
Major histocompatibility class II molecules (MHC class II), whose biosynthesis and expression by endothelial cells can be induced by gamma-interferon (IFN-gamma), play a major role in antigen recognition and subsequent cell-cell interactions involved in the initiation of immune responses. Adhesion molecules such as E-selectin and intercellular adhesion molecules (ICAM-1), whose biosynthesis and membrane expression by endothelial cells is regulated by proinflammatory cytokines (IL-1 and TNF), are necessary for the attachment and subsequent extravasation of leukocytes into the surrounding tissue. In the present study, the effects of preformed inflammatory mediators (histamine and serotonin) on the induction and expression of MHC class II, E-selectin, and ICAM-1 molecules by human umbilical vein endothelial cells were examined. Serotonin but not histamine was found to significantly inhibit in a dose-response fashion the induction and expression of MHC class II molecules. Inhibition occurred when it was added 24 h before, at the same time (most effective), or 24 h after IFN-gamma stimulation. No enhancement or stimulation of MHC class II biosynthesis could be detected using moderate or low concentration of either histamine or serotonin alone. In contrast to MHC class II molecules, neither serotonin nor histamine blocked the induction and biosynthesis of E-selectin and ICAM-1 molecules as detected by specific H18/7 and RR1/1 monoclonal antibodies, respectively, using flow cytometry. These findings suggest that serotonin but not histamine can assist in regulating the induction and expression of MHC class II molecules. Failure to block biosynthesis of E-selectin and ICAM-1 induced by TNF-alpha and IL-1 beta indicates the inhibitory effect exerted by serotonin was selective in nature.
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Department of Physiology and Biophysics, School of Medicine, University of Louisville, Ky 40202, USA.
Joshua
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Lian
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Justus
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D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology*; D006632:Histamine / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D011994:Recombinant Proteins; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D012701:Serotonin; D006632:Histamine; D007371:Interferon-gamma