Acute inflammatory reactions caused by histamine via monocytes/macrophages chronically participate in the initiation and progression of atherosclerosis

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.