Regulation of cellular and molecular trafficking across human brain endothelial cells by Th1- and Th2-polarized lymphocytes
Regulation of cellular and molecular trafficking across human brain endothelial cells by Th1- and Th2-polarized lymphocytes
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DOI：
10.1093/jnen/63.3.223
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发表时间：
2004-03-01
影响因子：
3.2
通讯作者：
Antel, JP
中科院分区：
文献类型：
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作者：
Biernacki, K;Prat, A;Antel, JP
我们使用成人脑源性内皮细胞(HBECs)来模拟外周血淋巴细胞跨血脑屏障(BBB)的迁移，就像MS所发生的那样。我们证明了抗IFNGamma抗体只能部分逆转同种异体或髓鞘碱性蛋白反应性Th1细胞的培养上清液诱导的HBECs诱导的黏附分子ICAM-1的表达增强和趋化因子CXCL10/IP-10、CCL2/MCP-1和CXCL8/IL-8的产生。这种效应不能单独用干扰素或肿瘤坏死因子α复制，这意味着在整体功能反应中有多种因素的相互作用。Th2细胞的培养上清既不能抑制也不能放大Th1诱导的效应。尽管Th1和Th2上清液可调节紧密连接分子ZO-1和ZO-2的表达和定位，但两者均不能改变HBEC单层对白蛋白的通透性，也不能增加随后的T细胞迁移率。Th1或Th2细胞先前在HBECs间的迁移确实促进了随后细胞和可溶性分子的通过。我们的结果表明，Th1或Th2极化的淋巴细胞在血脑屏障中的初始渗透有助于中枢神经系统炎症反应的持续。
We used adult human brain-derived endothelial cells (HBECs) to model migration of peripheral blood lymphocytes across the blood brain barrier (BBB) as occurs in MS. We demonstrate that enhanced expression of adhesion molecule ICAM-1 and production of chemokines CXCL10/IP-10, CCL2/MCP-1, and CXCL8/IL-8 by HBECs induced by supernatants derived from allogeneic or myelin basic protein-reactive Th1 cells is only partially reversed with anti-IFNgamma antibody. This effect is not reproduced with IFNgamma or TNFalpha alone, implicating the interaction of multiple factors in the overall functional response. Supernatants from Th2 cells neither suppressed nor amplified Th1-induced effects. Although both Th1 and Th2 supernatants modulated the expression and localization of tight junction molecules zonula occludens (ZO)-1 and ZO-2, neither supernatant altered the permeability of HBEC monolayers to albumin or increased subsequent T cell migration rates. Prior migration of Th1 or Th2 cells across HBECs did enhance subsequent passage of cells and soluble molecules. Our results suggest that initial infiltration of either Th1 or Th2 polarized lymphocytes across the BBB contributes to the continuation of an inflammatory response in the central nervous system.