Smooth muscle cells in human atherosclerotic plaques express the fractalkine receptor CX3CR1 and undergo chemotaxis to the CX3C chemokine fractalkine (CX3CL1)
Smooth muscle cells in human atherosclerotic plaques express the fractalkine receptor CX3CR1 and undergo chemotaxis to the CX3C chemokine fractalkine (CX3CL1)
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DOI：
10.1161/01.cir.0000097119.57756.ef
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发表时间：
2003-11-18
期刊：
影响因子：
37.8
通讯作者：
Greaves, DR
中科院分区：
文献类型：
--
作者：
Lucas, AD;Bursill, C;Greaves, DR
趋化因子是炎症细胞募集的重要介质，在动脉粥样硬化中发挥重要作用。Fractalkine （CX(3)CL1）是一种罕见的膜结合趋化因子，通过CX(3)CR1受体介导趋化。最近，人类CX3CR1基因的功能多态性被描述为与冠状动脉疾病相关。方法与结果采用免疫细胞术研究CX3C趋化因子fractalkine及其受体CX(3)CR1在人冠状动脉斑块中的表达。我们发现，在人类冠状动脉粥样硬化斑块中，单个核细胞的一个亚群表达高水平的fractalkine，而新内膜内的平滑肌细胞表达fractalkine受体CX(3)CR1。人动脉粥样硬化斑块中表达fractalgene的细胞数量与CX(3) cr1阳性细胞数量呈正相关（r=0.70, n=15个斑块）。此外，我们证明了培养的血管平滑肌细胞表达CX(3)CR1受体，并对fractalkine具有趋化性，这种趋化性可以被百日咳毒素的G蛋白失活所抑制。结论：这些结果表明，在人类动脉粥样硬化中，fractalkine可以作为平滑肌细胞迁移的介质，而不是介导炎症细胞募集。
Background-Chemokines are important mediators of inflammatory cell recruitment that play a significant role in atherosclerosis. Fractalkine (CX(3)CL1) is an unusual membrane-bound chemokine that mediates chemotaxis through the CX(3)CR1 receptor. Recently, functional polymorphisms in the human CX3CR1 gene have been described that are associated with coronary artery disease.Methods and Results-We investigated the expression of the CX3C chemokine fractalkine and its receptor CX(3)CR1 in human coronary artery plaques by immunocytometry. We show that a subset of mononuclear cells expresses high levels of fractalkine in human coronary atherosclerotic plaques and that smooth muscle cells within the neointima express the fractalkine receptor CX(3)CR1. There is a positive correlation between the number of fractalkine-expressing cells and the number of CX(3)CR1-positive cells in human atherosclerotic plaques (r=0.70, n=15 plaques). Furthermore, we demonstrate that cultured vascular smooth muscle cells express the CX(3)CR1 receptor and undergo chemotaxis to fractalkine that can be inhibited by G protein inactivation by pertussis toxin.Conclusions-These results suggest that in human atherosclerosis, fractalkine, rather than mediating inflammatory cell recruitment, can act as a mediator of smooth muscle cell migration.