Cytosolic phospholipase A2 alpha-deficient mice are resistant to experimental autoimmune encephalomyelitis.
Cytosolic phospholipase A2 alpha-deficient mice are resistant to experimental autoimmune encephalomyelitis.
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缺乏实验性自身免疫性脑脊髓炎的胞质磷脂酶A2α缺陷型小鼠具有抗性。
DOI：
10.1084/jem.20050665
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发表时间：
2005-09-19
影响因子：
15.3
通讯作者：
Clark, JD
中科院分区：
文献类型：
--
作者：
Marusic, S;Leach, MW;Pelker, JW;Azoitei, ML;Uozumi, N;Cui, JQ;Shen, MWH;DeClercq, CM;Miyashiro, JS;Carito, BA;Thakker, P;Simmons, DL;Leonard, JP;Shimizu, T;Clark, JD
实验性自身免疫性脑脊髓炎（EAE）是一种Th 1介导的中枢神经系统（CNS）炎症性疾病，是人类多发性硬化症的模型。胞浆型磷脂酶A2 α（cPLA 2 α）可启动EAE病变中的肾上腺素、白三烯和血小板活化因子的产生。使用髓鞘少突胶质细胞糖蛋白（MOG）免疫以及过继转移模型，我们表明cPLA 2 α −/−小鼠对EAE具有抗性。MOG免疫小鼠的CNS组织学检查显示cPLA 2 α +/−小鼠中存在广泛的炎性病变，而cPLA 2 α −/−小鼠中的病变大大减少或完全不存在。与cPLA 2 α +/−小鼠相比，WT小鼠产生的MOG特异性T细胞在cPLA 2 α −/−小鼠中诱导的EAE较轻，这表明cPLA 2 α在EAE的效应期发挥作用。此外，来自cPLA 2 α −/−小鼠的MOG特异性T细胞转移到WT小鼠中，与对照细胞诱导的EAE相比，诱导的EAE具有延迟发作和较低的严重程度;这表明cPLA 2 α在EAE的诱导阶段也起作用。来自cPLA 2 α −/−小鼠的MOG特异性T细胞缺乏Th 1型细胞因子的产生。与这种缺陷相一致的是，体内给予IL-12使cPLA 2 α −/−小鼠对EAE易感。我们的数据表明，cPLA 2 α在EAE的发展中起着重要作用，并促进T细胞向Th 1表型分化。
Experimental autoimmune encephalomyelitis (EAE), a Th1-mediated inflammatory disease of the central nervous system (CNS), is a model of human multiple sclerosis. Cytosolic phospholipase A2 α (cPLA2 α), which initiates production of prostaglandins, leukotrienes, and platelet-activating factor, is present in EAE lesions. Using myelin oligodendrocyte glycoprotein (MOG) immunization, as well as an adoptive transfer model, we showed that cPLA2 α −/− mice are resistant to EAE. Histologic examination of the CNS from MOG-immunized mice revealed extensive inflammatory lesions in the cPLA2 α +/− mice, whereas the lesions in cPLA2 α −/− mice were reduced greatly or completely absent. MOG-specific T cells generated from WT mice induced less severe EAE in cPLA2 α −/− mice compared with cPLA2 α +/− mice, which indicates that cPLA2 α plays a role in the effector phase of EAE. Additionally, MOG-specific T cells from cPLA2 α −/− mice, transferred into WT mice, induced EAE with delayed onset and lower severity compared with EAE that was induced by control cells; this indicates that cPLA2 α also plays a role in the induction phase of EAE. MOG-specific T cells from cPLA2 α −/− mice were deficient in production of Th1-type cytokines. Consistent with this deficiency, in vivo administration of IL-12 rendered cPLA2 α −/− mice susceptible to EAE. Our data indicate that cPLA2 α plays an important role in EAE development and facilitates differentiation of T cells toward the Th1 phenotype.
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影响因子：
4.8
作者：
Locati, M;Lamorte, G;Sozzani, S
通讯作者：
Sozzani, S
DOI：
10.1084/jem.181.1.381
发表时间：
1995-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Leonard JP;Waldburger KE;Goldman SJ
通讯作者：
Goldman SJ
影响因子：
4.4
作者：
Harizi, H;Juzan, M;Gualde, N
通讯作者：
Gualde, N
影响因子：
64.8
作者：
Huang, JT;Welch, JS;Glass, CK
通讯作者：
Glass, CK
影响因子：
5.4
作者：
LININGTON, C;BERGER, T;WEKERLE, H
通讯作者：
WEKERLE, H