CD40 Mediates Retinal Inflammation and Neurovascular Degeneration
CD40 Mediates Retinal Inflammation and Neurovascular Degeneration
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DOI：
10.4049/jimmunol.181.12.8719
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发表时间：
2008-12-15
影响因子：
4.4
通讯作者：
Subauste, Carlos S.
中科院分区：
文献类型：
--
作者：
Portillo, Jose-Andres C.;Van Grol, Jennifer;Subauste, Carlos S.
视网膜病变是视力损害的主要原因。我们使用缺血性视网膜病变模型来研究CD 40在视网膜损伤发病机制中的作用。在CD 40（-/-）小鼠的缺血视网膜中，视网膜炎症、神经节细胞丢失和毛细血管变性明显减弱。CD 40（-/-）小鼠视网膜缺血后NOS 2和COX 2的上调减弱。野生型小鼠缺血性视网膜中NOS 2-考克斯-2的上调至少部分是由NOS 2（+）考克斯-2（+）白细胞的募集来解释的。KC/CXCL 1和ICAM-1的上调也需要CD 40。视网膜内皮细胞和Muller细胞表达CD 40。通过CD 40刺激这些细胞引起ICAM-1上调和KC/CXCL 1产生。骨髓移植实验表明，视网膜缺血后白细胞浸润，神经节细胞损失，促炎分子的上调依赖于视网膜中的CD 40表达，而不是外周血白细胞。这些研究将CD 40鉴定为视网膜炎症和神经血管变性的调节剂。他们支持一种模型，其中内皮细胞和Muller细胞的CD 40刺激触发粘附分子上调和趋化因子产生，促进表达NOS 2/考克斯-2（与神经血管变性相关的分子）的白细胞的募集。免疫学杂志，2008，181：8719-8726.
Retinopathies are major causes of visual impairment. We used a model of ischemic retinopathy to examine the role of CD40 in the pathogenesis of retinal injury. Retinal inflammation, loss of ganglion cells, and capillary degeneration were markedly attenuated in ischemic retinas of CD40(-/-) mice. Up-regulation of NOS2 and COX2 after retinal ischemia were blunted in CD40(-/-) mice. NOS2-COX-2 up-regulation in ischemic retinas from wild-type mice was at least in part explained by recruitment of NOS2(+)COX-2(+) leukocytes. Up-regulation of KC/CXCL1 and ICAM-1 also required CD40. Retinal endothelial and Muller cells expressed CD40. Stimulation of these cells through CD40 caused ICAM-1 up-regulation and KC/CXCL1 production. Bone marrow transplant experiments revealed that leukocyte infiltration, ganglion cell loss, and up-regulation of proinflammatory molecules after retinal ischemia were dependent on CD40 expression in the retina and not peripheral blood leukocytes. These studies Identified CD40 as a regulator of retinal inflammation and, neurovascular degeneration. They support a model in which CD40 stimulation of endothelial and Muller cells triggers adhesion molecule up-regulation and chemokine production, promoting the recruitment of leukocytes that express NOS2/COX-2, molecules linked to neurovascular degeneration. The Journal of Immunology, 2008, 181: 8719-8726.