Shamri Revital, Grabovsky Valentin, Gauguet Jean-Marc, Feigelson Sara, Manevich Eugenia, Kolanus Waldemar, Robinson Martyn K, Staunton Donald E, von Andrian Ulrich H, Alon Ronen
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Nat Immunol. 2005 May;6(5):497-506. doi: 10.1038/ni1194. Epub 2005 Apr 17.
It is widely believed that rolling lymphocytes require successive chemokine-induced signaling for lymphocyte function-associated antigen 1 (LFA-1) to achieve a threshold avidity that will mediate lymphocyte arrest. Using an in vivo model of lymphocyte arrest, we show here that LFA-1-mediated arrest of lymphocytes rolling on high endothelial venules bearing LFA-1 ligands and chemokines was abrupt. In vitro flow chamber models showed that endothelium-presented but not soluble chemokines triggered instantaneous extension of bent LFA-1 in the absence of LFA-1 ligand engagement. To support lymphocyte adhesion, this extended LFA-1 conformation required immediate activation by its ligand, intercellular adhesion molecule 1. These data show that chemokine-triggered lymphocyte adhesiveness involves a previously unrecognized extension step that primes LFA-1 for ligand binding and firm adhesion.
人们普遍认为，滚动的淋巴细胞需要连续的趋化因子诱导信号，以使淋巴细胞功能相关抗原1（LFA-1）达到介导淋巴细胞停滞的阈值亲和力。利用淋巴细胞停滞的体内模型，我们在此表明，LFA-1介导的在带有LFA-1配体和趋化因子的高内皮微静脉上滚动的淋巴细胞的停滞是突然的。体外流动腔模型表明，内皮细胞呈现而非可溶性趋化因子在没有LFA-1配体结合的情况下触发弯曲的LFA-1瞬间伸展。为了支持淋巴细胞黏附，这种伸展的LFA-1构象需要其配体细胞间黏附分子1立即激活。这些数据表明，趋化因子触发的淋巴细胞黏附涉及一个以前未被认识的伸展步骤，该步骤使LFA-1为配体结合和牢固黏附做好准备。
