title: Acute inflammatory reactions caused by histamine via monocytes/macrophages chronically participate in the initiation and progression of atherosclerosis.
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.
authors.affiliation: Department of Pathology and Cell Biology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Ke-Yong
authors.initials: KY
authors.lastname: Wang
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Murata
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Nakashima
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
mesh_terms: D001011:Aorta; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D006633:Histamine Antagonists; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D006632:Histamine; D013755:Tetradecanoylphorbol Acetate