Lyck Ruth, Reiss Yvonne, Gerwin Nicole, Greenwood John, Adamson Peter, Engelhardt Britta
Max-Planck-Institute for Physiological and Clinical Research, W G Kerckhoff Institute, Bad Neuheim, Germany.
Blood. 2003 Nov 15;102(10):3675-83. doi: 10.1182/blood-2003-02-0358. Epub 2003 Jul 31.
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-expression of different ICAM-1 mutants in the ICAM-1-/-ICAM-2-/- endothelioma line bEndI1/2.1 or in the ICAM-1-/- endothelioma line bEndI1.1 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.
内皮细胞间黏附分子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细胞外渗过程中的具体作用，我们使用了小鼠T细胞和ICAM-1基因敲除/ICAM-2基因敲除的脑内皮瘤细胞。ICAM-1基因敲除/ICAM-2基因敲除的脑内皮瘤细胞在体外不支持T细胞的跨内皮迁移（TEM）。在ICAM-1基因敲除/ICAM-2基因敲除的内皮瘤细胞系bEndI1/2.1或ICAM-1基因敲除的内皮瘤细胞系bEndI1.1中重新表达不同的ICAM-1突变体，结果表明ICAM-1的胞外结构域足以支持T细胞黏附，而TEM则严格需要胞质尾的存在。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（RhoGTPase）激活并非必需。此外，ICAM-1的胞质缺失突变体无法介导RhoGTPase激活。因此，我们的数据表明，内皮ICAM-1的胞质尾独立于酪氨酸磷酸化对于支持T淋巴细胞的TEM至关重要，而Rho信号传导则在内皮细胞中起作用。
