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Published Online
on October 28, 2004

Arteriosclerosis, Thrombosis, and Vascular Biology. 2004
Published online before print October 28, 2004, doi: 10.1161/01.ATV.0000148705.13411.65
A more recent version of this article appeared on February 1, 2005
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Medline Plus Health Information
*Carotid Artery Disease
Hazardous Substances DB
*HISTAMINE

Submitted on November 13, 2003
Accepted on October 3, 2004

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 ; and 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.

* To whom correspondence should be addressed. 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.
Key words: monocyte/macrophage • histamine • histidine decarboxylase • histamine receptor • atherosclerosis




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