Blood cell-derived RANTES mediates cerebral microvascular dysfunction, inflammation, and tissue injury after focal ischemia-reperfusion.
Blood cell-derived RANTES mediates cerebral microvascular dysfunction, inflammation, and tissue injury after focal ischemia-reperfusion.
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DOI：
10.1161/strokeaha.107.513150
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发表时间：
2008-09
期刊：
影响因子：
8.3
通讯作者：
Granger DN
中科院分区：
文献类型：
--
作者：
Terao S;Yilmaz G;Stokes KY;Russell J;Ishikawa M;Kawase T;Granger DN
虽然趋化因子与心血管疾病有关，但很少有研究涉及这些炎症介质在缺血性卒中中的作用。本研究验证了RANTES（CCL 5;在激活后调节，正常T细胞表达和分泌）介导脑缺血和再灌注（I/R）诱导的脑微血管功能障碍、炎症和组织损伤的假设。在大脑中动脉闭塞和再灌注（MCAO/R）60分钟后，在野生型小鼠（WT）、RANTES缺陷小鼠（RANTES-/-）、移植RANTES-/-骨髓的WT小鼠（RANTES>WT）和对照骨髓嵌合体（WT>WT）中测量脑小静脉中白细胞和血小板的粘附、梗死体积和血脑屏障（BBB）通透性。RANTES和几种细胞因子的浓度也通过ELISA和流式细胞仪珠阵列测量。在RANTES−/−小鼠中，MCAO/R后WT和WT>WT小鼠中引起的白细胞和血小板粘附增强、BBB通透性增加和组织梗死显著减弱。在RANTES>WT嵌合体中观察到MCAO/R诱导的应答的类似衰减。虽然RANTES缺乏没有改变由MCAO/R引起的组织细胞因子水平的变化，但血浆浓度IL-6、IL-10和IL-12均降低。这些发现暗示血细胞来源的RANTES在脑缺血和再灌注的微血管、炎症和组织损伤反应中。
While chemokines have been implicated in cardiovascular diseases, few studies have addressed the role of these inflammatory mediators in ischemic stroke. This study tested the hypothesis that RANTES (CCL5; regulated upon activation, normal T-cell expressed and secreted) mediates the cerebral microvascular dysfunction, inflammation and tissue injury induced by brain ischemia and reperfusion (I/R). Following 60 minute middle cerebral artery occlusion and reperfusion (MCAO/R), the adhesion of leukocytes and platelets in cerebral venules, infarct volume and blood-brain barrier (BBB) permeability were measured in wild type mice (WT), RANTES-deficient mice (RANTES−/−), WT mice transplanted with RANTES−/− bone marrow (RANTES>WT) and control bone marrow chimeras (WT>WT). The concentration of RANTES and several cytokines was also measured by ELISA and a cytometric bead array. The enhanced leukocyte and platelet adhesion, increased BBB permeability, and tissue infarction elicited in WT and WT>WT mice after MCAO/R were significantly blunted in RANTES−/− mice. Similar attenuation of the MCAO/R-induced responses were noted in RANTES>WT chimeras. While RANTES deficiency did not alter the changes in tissue cytokine levels elicited by MCAO/R, plasma concentrations IL-6, IL-10 and IL-12 were all reduced. These findings implicate blood cell-derived RANTES in the microvascular, inflammatory and tissue injury responses of the brain to ischemia and reperfusion.