Abstract
Previously we demonstrated that histidine decarboxylase (HDC), which produces histamine from l-histidine, was detected in monocytes/macrophages located in human atherosclerotic lesions. As monocytic migration is a key event of atherogenesis, we investigated whether histamine induces monocytic expression of monocyte chemoattractant protein (MCP)-1 and its receptors CCR2-A and -B, and also endothelial expression of ICAM-1 and VCAM-1. Furthermore, we studied the effect of interleukin (IL)-4, which inhibits the HDC expression, on the expression of MCP-1 and CCR2. Histamine stimulated monocytes, but not macrophages, to express MCP-1 and CCR2-A and -B. The expression of MCP-1 was inhibited by histamine H2 blocker. In contrast, IL-4 enhanced CCR2 expression but not MCP-1. Histamine stimulated endothelial cells to express ICAM-1 and VCAM-1. These results indicate that histamine and IL-4, which are both synthesized in the arterial intima, chronically participates in the pathogenesis of atherosclerosis via the enhanced expression of monocytic MCP-1, CCR2 and endothelial adhesion molecules.
MeSH terms
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Aorta
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Arteriosclerosis / etiology
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Arteriosclerosis / metabolism*
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Cell Line, Transformed
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Cell Line, Tumor
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Chemokine CCL2 / biosynthesis*
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Chemokine CCL2 / genetics
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Dose-Response Relationship, Drug
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Endothelium, Vascular / cytology
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Fluorescent Antibody Technique, Indirect
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Gene Expression / drug effects
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Histamine / pharmacology*
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Histamine Antagonists / pharmacology
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Humans
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Intercellular Adhesion Molecule-1 / biosynthesis
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Interleukin-4 / pharmacology
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Macrophages / drug effects*
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Macrophages / metabolism
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Monocytes / drug effects*
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Monocytes / metabolism
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RNA, Messenger / metabolism
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Receptors, CCR2
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Receptors, Chemokine / biosynthesis*
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Receptors, Chemokine / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Tetradecanoylphorbol Acetate / pharmacology
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Up-Regulation
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Vascular Cell Adhesion Molecule-1 / biosynthesis
Substances
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CCL2 protein, human
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CCR2 protein, human
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Chemokine CCL2
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Histamine Antagonists
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RNA, Messenger
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Receptors, CCR2
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Receptors, Chemokine
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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Interleukin-4
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Histamine
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Tetradecanoylphorbol Acetate