T-cell interaction with ICAM-1/ICAM-2 double-deficient brain endothelium in vitro: the cytoplasmic tail of endothelial ICAM-1 is necessary for transendothelial migration of T cells
T-cell interaction with ICAM-1/ICAM-2 double-deficient brain endothelium in vitro: the cytoplasmic tail of endothelial ICAM-1 is necessary for transendothelial migration of T cells
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DOI：
10.1182/blood-2003-02-0358
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发表时间：
2003-11-15
期刊：
影响因子：
20.3
通讯作者：
Engelhardt, B
中科院分区：
文献类型：
--
作者：
Lyck, R;Reiss, Y;Engelhardt, B
内皮细胞间粘附分子1（ICAM-1）和ICAM-2均参与免疫监视和炎症过程中的淋巴细胞外渗。为了确定它们在T细胞外渗过程中的确切作用，我们使用小鼠T细胞和ICAM-1（-/-）ICAM-2（-/-）脑内皮瘤细胞。ICAM-1（-/-）ICAM-2（-/-）脑内皮瘤细胞在体外不支持T细胞的跨内皮迁移（TEM）。不同ICAM-1突变体在ICAM-1（-/-）ICAM-2（-/-）内皮瘤细胞系bEndl 1/2.1或ICAM-1（-/-）内皮瘤细胞系bEndl1.1中的再表达表明，ICAM-1的细胞外结构域足以支持T细胞粘附，而细胞质尾区的存在是TEM的严格要求。令人惊讶的是，内皮ICAM-1的酪氨酸磷酸化对于T细胞的TEM或Rho鸟苷三磷酸酶（RhoGTdR）活化不是必需的。此外，ICAM-1的细胞质缺失突变体不能介导RhoGT 3激活。因此，我们的数据表明，内皮细胞间粘附分子-1的胞质尾-独立于酪氨酸磷酸化-是必不可少的支持TEM的T淋巴细胞，而Rho信号参与内皮细胞。(C)2003年，美国血液学会。
Endothelial intercellular adhesion molecule 1 (ICAM-1) and ICAM-2 are both involved in lymphocyte extravasation during immunosurveillance and inflammation. To define their exact role during T-cell extravasation, we used mouse T cells and ICAM-1(-/-)ICAM-2(-/-) brain endothelioma cells. ICAM-1(-/-)ICAM-2(-/-) brain endothelioma cells did not support transendothelial migration (TEM) of T cells in vitro. Re-exprelssion of different ICAM-1 mutants in the ICAM-1(-/-)ICAM-2(-/-) endothelioma line bEndl1/2.1 or in the ICAM1(-/-) endothelioma line bEndl1.1 demonstrated that the extracellular domain of ICAM-1 suffices to support T-cell adhesion while the presence of the cytoplasmic tail was strictly required for TEM. Surprisingly, tyrosine phosphorylation of endothelial ICAM-1 was not necessary for TEM of T cells or for Rho guanosine triphosphatase (RhoGTPase) activation. Furthermore, cytoplasmic deletion mutants of ICAM-1 were unable to mediate RhoGTPase activation. Thus, our data demonstrate that the cytoplasmic tail of endothelial ICAM-1-independently from tyrosine phosphorylation-is essential for supporting TEM of T lymphocytes, while Rho signaling is involved in endothelial cells. (C) 2003 by The American Society of Hematology.