Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus and activation-regulated chemokine, are expressed in human atherosclerotic lesions
Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus and activation-regulated chemokine, are expressed in human atherosclerotic lesions
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DOI：
10.1161/01.atv.21.6.923
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发表时间：
2001-06-01
影响因子：
8.7
通讯作者：
Ylä-Hertualla, S
中科院分区：
文献类型：
--
作者：
Greaves, DR;Häkkinen, T;Ylä-Hertualla, S
在许多炎症病理中，趋化因子是巨噬细胞和t细胞募集的重要介质，在动脉粥样硬化病变中表达的趋化因子可能在单核细胞募集和巨噬细胞分化中发挥重要作用。我们通过逆转录聚合酶链反应和免疫组织化学分析了编码巨噬细胞来源趋化因子（MDC/CCL22）、胸腺和激活调节趋化因子（TARC/CCL17）和CX3C趋化因子fractalkine （CX(3)CL1）的连锁染色体16q13基因在原代巨噬细胞和人动脉粥样硬化病变中的表达。我们发现巨噬细胞中趋化因子MDC、fractalkine和TARC的表达在th2型细胞因子白介素-4和白介素-13的作用下上调。在一些患者中可以看到高水平的MDC、TARC和fractalkine mRNA表达。但并不是所有人的动脉都有严重的动脉粥样硬化病变。免疫组织化学表明，MDC、fractalkine和TARC是由含有斑块微血管的斑块区域内的巨噬细胞亚群表达的。我们得出结论，MDC、fractalkine和TARC是染色体16q13趋化因子，可能在单核细胞募集到动脉粥样硬化病变中发挥作用，并影响随后的炎症反应。白细胞介素-4上调巨噬细胞表达的趋化因子可能是人类动脉粥样硬化病变中th2型免疫反应存在的有用替代标志物。
Chemokines are important mediators of macrophage and T-cell recruitment in a number of inflammatory pathologies, and chemokines expressed in atherosclerotic lesions may play an important role in mononuclear cell recruitment and macrophage differentiation. We have analyzed the expression of the linked chromosome 16q13 genes that encode macrophage-derived chemokine (MDC/CCL22), thymus- and activation-regulated chemokine (TARC/CCL17), and the CX3C chemokine fractalkine (CX(3)CL1) in primary macrophages and human atherosclerotic lesions by reverse transcription-polymerase chain reaction and immunohistochemistry. We show that macrophage expression of the chemokines MDC, fractalkine, and TARC is upregulated by treatment with the Th2-type cytokines interleukin-4 and interleukin-13. High levels of MDC, TARC, and fractalkine mRNA expression are seen in some. but not all, human arteries with advanced atherosclerotic lesions. Immunohistochemistry shows that MDC, fractalkine, and TARC are expressed by a subset of macrophages within regions of plaques that contain plaque microvessels, We conclude that MDC, fractalkine, and TARC, which are chromosome 16q13 chemokines, could play a role in mononuclear cell recruitment into atherosclerotic lesions and influence the subsequent inflammatory response. Macrophage-expressed chemokines upregulated by interleukin-4 may be useful surrogate markers for the presence of Th2-type immune responses in human atherosclerotic lesions.