期刊
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
卷 459, 期 1, 页码 71-77出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00424-009-0710-y
关键词
Chemotaxis; Migration; Monocytes; LPC; MCP-1; Ion channels
类别
资金
- St. George's University of London
- Wellcome Trust
One of the earliest cellular responses in atherogenesis is the focal recruitment of circulating monocytes, while the most important atherogenic chemoattractants are monocyte chemoattractant protein-1 (MCP-1) and lysophosphatidylcholine (LPC). Invading monocytes transform into activated macrophages and foam cells, which stimulate inflammatory processes and promote atherosclerosis. In this study, we have searched for common mechanisms involved in MCP-1- and LPC-stimulated monocyte migration. We have found that migration of THP-1 monocytes stimulated with MCP-1 was reduced upon inhibition of G(i/o) proteins with pertussis toxin and upon inhibition of platelet activating factor receptors with BN52021, whereas LPC-stimulated monocyte chemotaxis remained unaffected by both inhibitors. Furthermore, Cl- channels were only required for MCP-1-induced chemotaxis. However, activity of voltage-gated K+ channels and of Ca2+-activated K+ channels was found to be involved in migration of monocytes stimulated with either MCP-1 or LPC. Inhibition of voltage-gated K+ channels with 4-aminopyridine or margatoxin partially inhibited MCP-1- and LPC-stimulated migration of monocytes. Blockade of Ca2+-activated K+ channels with TRAM-34 also partially reduced migration of MCP-1- and LPC-stimulated monocytes. Simultaneous inhibition of voltage-gated and Ca2+-activated K+ channels abolished MCP-1- and LPC-induced chemotaxis of monocytes. Thus, K+ channel inhibition may represent a novel powerful strategy to reduce monocyte infiltration and subsequent inflammation in atherosclerosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据