CXCR3 activation promotes lymphocyte transendothelial migration across human hepatic endothelium under fluid flow
CXCR3 activation promotes lymphocyte transendothelial migration across human hepatic endothelium under fluid flow
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DOI：
10.1016/s0002-9440(10)62060-3
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发表时间：
2005-09-01
影响因子：
6
通讯作者：
Adams, DH
中科院分区：
文献类型：
--
作者：
Curbishley, SM;Eksteen, B;Adams, DH
在趋化试验中，炎症肝脏中的T细胞表达高水平的CXCR3，并表现出向CXCR3配体迁移的增强。此外，CXCR3配体在慢性肝炎中T细胞浸润部位的肝内皮细胞上表达上调，其存在与炎症性肝病的转归有关。我们采用基于血流的人肝内皮细胞黏附实验，研究了在血流生理条件下，CXCR3在淋巴细胞与肝内皮细胞黏附和迁移中的作用。为了更准确地模拟体内激活的CXCR3(高)淋巴细胞的功能，我们从人肝组织中分离T细胞，并在基于流动的黏附试验中研究它们的行为。我们证明，CXCR3不仅促进效应T细胞与内皮细胞的黏附，而且还能推动内皮细胞的跨内皮迁移。此外，这些反应既可以被内皮分泌的内源性CXCR3配体刺激，也可以被来自其他类型细胞并由内皮呈现的外源性CXCR3配体刺激。因此，本研究表明，CXCR3的激活促进了淋巴细胞在血流条件下的黏附和跨内皮细胞迁移，人肝内皮细胞可以呈现由肝脏内其他类型的细胞分泌的功能性活性趋化因子。
T cells infiltrating the inflamed liver express high levels of CXCR3 and show enhanced migration to CXCR3 ligands in chemotactic assays. Moreover, CXCR3 ligands are up-regulated on hepatic endothelium at sites of T-cell infiltration in chronic hepatitis, and their presence correlates with outcome of inflammatory liver disease. We used a flow-based adhesion assay with human hepatic endothelium to investigate the function of CXCR3 on lymphocyte adhesion to and transmigration through hepatic endothelium under physiological conditions of blood flow. To more accurately model the function of in vivo activated CXCR3(high) lymphocytes, we isolated T cells from human liver tissue and studied their behavior in flow-based adhesion assays. We demonstrate that CXCR3 not only promoted the adhesion of effector T cells to endothelium from flow but also drove transendothelial migration. Moreover, these responses could be stimulated either by endogenous CXCR3 ligands secreted by the endothelium or by exogenous CXCR3 ligands derived from other cell types and presented by the endothelium. This study thus demonstrates that activation of CXCR3 promotes lymphocyte adhesion and transendothelial migration under flow and that human hepatic endothelium can present functionally active chemokines secreted by other cell types within the liver.