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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:430.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Granulocyte Macrophage–Colony Stimulating Factor Increases the Expression of Histamine and Histamine Receptors in Monocytes/Macrophages in Relation to Arteriosclerosis

Yoshitaka Murata; Akihide Tanimoto; Ke-Yong Wang; Masato Tsutsui; Yasuyuki Sasaguri; Filip De Corte; Hiroshi Matsushita

From the Kyurin Omtest Laboratory (Y.M.), Kyurin Corporation, Yahatanishi-ku, Kitakyushu, the Department of Pathology (A.T., H.M.), Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, and the Departments of Pathology and Cell Biology (A.T., K.-Y.W., Y.S.) and Pharmacology (M.T.), School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan; and Johnson and Johnson Pharmaceuticals Group (F.D.), Licensing and New Business Development, Beerse, Belgium.

Correspondence to Akihide Tanimoto, MD, PhD, Department of Pathology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan. E-mail aki{at}toranomon.gr.jp

Objective— To study the effect of granulocyte macrophage–colony-stimulating factor (GM-CSF) on histamine metabolism in arteriosclerosis, the expression of histidine decarboxylase (HDC; histamine-producing enzyme), histamine receptors 1 and 2 (HH1R and HH2R), and GM-CSF was investigated in human and mouse arteriosclerotic carotid arteries. Furthermore, the molecular mechanisms of GM-CSF–induced HDC and HH1R expression in monocytic U937 cells were investigated.

Methods and Results— Immunohistochemistry showed that atherosclerotic human coronary and mouse ligated carotid arteries contained HDC-expressing macrophages. Gene expression of HDC, HH1R, HH2R, and GM-CSF was also detected in the lesions. In U937 cells, GM-CSF enhanced histamine secretion and gene expression of HDC and HH1R. A promoter assay showed that GM-CSF enhanced gene transcription of HDC and HH1R but not HH2R.

Conclusion— The present results indicate that HDC and HHR are expressed in arteriosclerotic lesion, and that GM-CSF induces HDC and HH1R expression in monocytes. Locally produced histamine might participate in atherogenesis by affecting the expression of atherosclerosis-related genes in monocytes and smooth muscle cells.

The presence of histamine-producing macrophages and gene expression of histamine receptors and GM-CSF was demonstrated in arteriosclerotic lesions. In monocytic U937 cells, GM-CSF upregulated the expression of histamine and HH1R. Coordinated expression of histamine and its receptors by GM-CSF would participate in atherogenesis by affecting monocytic and SMC gene expression.

Key Words: monocyte/macrophage • histamine • histidine decarboxylase • histamine receptor • atherosclerosis

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