E- and P-selectin are not required for the development of experimental autoimmune encephalomyelitis in C57BL/6 and SJL mice
E- and P-selectin are not required for the development of experimental autoimmune encephalomyelitis in C57BL/6 and SJL mice
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DOI：
10.4049/jimmunol.179.12.8470
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发表时间：
2007-12-15
影响因子：
4.4
通讯作者：
Engelhardt, Britta
中科院分区：
文献类型：
--
作者：
Doering, Axinia;Wild, Martin;Engelhardt, Britta
在多发性硬化症及其实验性自身免疫性脑脊髓炎（EAE）动物模型中，炎性细胞迁移穿过内皮血脑屏障（BBB）并进入CNS。已经确定α（4）整联蛋白在EAE期间积极参与白细胞通过BBB的募集。相比之下，内皮E-和P-选择素在这一过程中的作用一直是一个有争议的问题。在这项研究中，我们证明，P-选择素蛋白可以检测到脑膜血管内皮细胞在健康的SJL和C5713 L/6小鼠和罕见的实质CNS血管在C57 BL/6，但不是SJL，小鼠。在EAE过程中，P-选择素，但不是E-选择素的表达被发现上调炎症浸润周围的炎症CNS微血管，无论其脑膜或实质定位与更突出的免疫染色检测C57 BL/6相比，SJL小鼠。P-选择素免疫染色可定位于CNS内皮细胞和粘附于血管壁的CD 41阳性血小板。尽管野生型小鼠中存在P-选择素，但E/P-选择素缺陷型SJL和C57 BL/6小鼠发生的临床EAE与野生型小鼠难以区分。E-和P-选择素的缺乏既不影响髓鞘特异性T细胞的活化，也不影响EAE期间CNS中细胞浸润的组成。最后，在转基因C57 BL/6小鼠中，内皮特异性四环素诱导的E-选择素在BBB的表达并没有改变EAE的发展。因此，在C57 BL/6和SJL小鼠中，E-和P-选择素对于跨越BBB的白细胞募集和EAE的发展不是必需的。
In multiple sclerosis and in its animal model experimental autoimmune encephalomyelitis (EAE), inflammatory cells migrate across the endothelial blood-brain barrier (BBB) and gain access to the CNS. It is well -established that alpha(4) integrins are actively involved in leukocyte recruitment across the BBB during EAE. In contrast, the role of endothelial E- and P-selectin in this process has been a controversial issue. In this study, we demonstrate that P-selectin protein can be detected in meningeal blood vessel endothelial cells in healthy SJL and C5713L/6 mice and on rare parenchymal CNS blood vessels in C57BL/6, but not SJL, mice. During EAE, expression of P-selectin but not E-selectin was found up-regulated on inflamed CNS microvessels surrounded by inflammatory infiltrates irrespective of their meningeal or parenchymal localization with a more prominent immunostaining detected in C57BL/6 as compared with SJL mice. P-selectin immumostaining could be localized to CNS endothelial cells and to CD41-positive platelets adhering to the vessel wall. Despite the presence of P-selectin in wild-type mice, E/P-selectin-deficient SJL and C57BL/6 mice developed clinical EAE indistinguishable from wild-type mice. Absence of E- and P-selectin did neither influence the activation of myelin-specific T cells nor the composition of the cellular infiltrates in the CNS during EAE. Finally, endothelial-specific tetracycline-inducible expression of E-selectin at the BBB in transgenic C57BL/6 mice did not alter the development of EAE. Thus, E- and P-selectin are not required for leukocyte recruitment across the BBB and the development of EAE in C57BL/6 and in SJL mice.