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

Y. Murata
2004 Arteriosclerosis, Thrombosis and Vascular Biology  
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
more » ... ts-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. (Arterioscler Thromb Vasc Biol. 2005;25:430-435.)
doi:10.1161/01.atv.0000148705.13411.65 pmid:15514212 fatcat:ct5kgra6lnbntf6menua72mkoq