Granulocyte macrophage-colony stimulating factor increases the expression of histamine and histamine receptors in monocytes/macrophages in relation to arteriosclerosis
Granulocyte macrophage-colony stimulating factor increases the expression of histamine and histamine receptors in monocytes/macrophages in relation to arteriosclerosis
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DOI：
10.1161/01.atv.0000148705.13411.65
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发表时间：
2005-02-01
影响因子：
8.7
通讯作者：
Matsushita, H
中科院分区：
文献类型：
--
作者：
Murata, Y;Tanimoto, A;Matsushita, H
目的研究人和小鼠颈动脉组织中组胺产生酶（histamine decarboxylase，HDC）、组胺受体1（histamine receptor 1，HH 1 R）、组胺受体2（histamine receptor 2，HH 2 R）和粒细胞巨噬细胞集落刺激因子（granulocytemacrophage-colony-stimulating factor，GM-CSF）的表达，探讨GM-CSF对动脉硬化中组胺代谢的影响。此外，GM-CSF诱导的HDC和HH 1 R在单核细胞U937 cells中表达的分子机制进行了调查。方法和结果-免疫组织化学显示，动脉粥样硬化的人冠状动脉和小鼠结扎的颈动脉中含有表达HDC的巨噬细胞。HDC、HH 1 R、HH 2 R和GM-CSF基因在病变中也有表达。在U937细胞中，GM-CSF促进HDC和HH 1 R的组胺分泌和基因表达。启动子分析显示，GM-CSF可促进HDC和HH 1 R基因的转录，但对HH 2 R基因的转录无明显影响。结论：动脉粥样硬化病变中存在HDC和HHR基因的表达，GM-CSF可诱导单核细胞表达HDC和HH 1 R基因。局部产生的组胺可能通过影响单核细胞和平滑肌细胞中动脉粥样硬化相关基因的表达而参与动脉粥样硬化的形成。
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.