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      Histamine downregulates CD14 expression via H2 receptors on human monocytes.

      Clinical Immunology (Orlando, Fla.)
      Antigens, CD14, metabolism, Cells, Cultured, Dimaprit, pharmacology, Down-Regulation, Histamine, physiology, Histamine Agonists, Histamine H2 Antagonists, Humans, Leukocytes, Mononuclear, Lipopolysaccharides, Methylhistamines, Monocytes, drug effects, Receptors, Histamine H2, Time Factors, Tumor Necrosis Factor-alpha, antagonists & inhibitors, biosynthesis

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          Abstract

          Lipopolysaccharide (LPS) binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14 on human monocyte. LPS is transferred to the transmembrane signaling receptor toll-like receptor (TLR) 4. In the present study, the effect of histamine on the expression of CD14 on human monocytes was investigated. Histamine concentration- and time-dependently decreased the expression of cell surface CD14, whereas histamine did not decrease mRNA for CD14 nor increase soluble CD14 (sCD14). The inhibitory effects of histamine on CD14 expression were antagonized by H2-receptor antagonist, but not by H1 and H3/H4 antagonist. The effects of selective H2-receptor agonists, 4-methylhistamine and dimaprit, on CD14 expression mimicked that of histamine indicating that histamine regulated CD14 expression through the stimulation of H2-receptors. The pretreatment with histamine partially inhibited the LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMC). Such inhibition might be due to the down-regulation of CD14 expression on monocytes by histamine.

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