Foy D S, Ley K
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville, Virginia 22908, USA.
Microvasc Res. 2000 Nov;60(3):249-60. doi: 10.1006/mvre.2000.2272.
The leukocyte integrins LFA-1 and Mac-1 bind to endothelial intercellular adhesion molecule-1 (ICAM-1). Leukocyte adhesion induced by micropipette injection of formylmethionylleucylphenylalanine (fMLP) or macrophage inflammatory protein 2 (MIP-2) next to a venule in the exteriorized mouse cremaster muscle was almost completely blocked after intravenous injection of the ICAM-1 mAb YN-1. In contrast, after 2-h pretreatment with TNF-alpha, leukocyte adhesion induced in postcapillary venules by fMLP or MIP-2 was not blocked by the ICAM-1 mAb. Leukocyte adhesion was significantly reduced by mAb GAME-46 to CD18 even after TNF-alpha treatment. We conclude that ICAM-1 is necessary for neutrophil adhesion to unstimulated endothelium, but not for adhesion to cytokine-stimulated endothelium. Although ICAM-1 is expressed at high levels after TNF-alpha, ICAM-1 either is not functional or is redundant with other endothelial ligands for beta(2) integrins.
白细胞整合素LFA-1和Mac-1与内皮细胞间黏附分子-1（ICAM-1）结合。在外翻的小鼠提睾肌微静脉旁通过微量移液器注射甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）或巨噬细胞炎性蛋白2（MIP-2）诱导的白细胞黏附，在静脉注射ICAM-1单克隆抗体YN-1后几乎完全被阻断。相比之下，用肿瘤坏死因子-α（TNF-α）预处理2小时后，fMLP或MIP-2在毛细血管后微静脉中诱导的白细胞黏附未被ICAM-1单克隆抗体阻断。即使经过TNF-α处理，抗CD18单克隆抗体GAME-46也能显著降低白细胞黏附。我们得出结论，ICAM-1是中性粒细胞黏附于未受刺激内皮细胞所必需的，但不是黏附于细胞因子刺激的内皮细胞所必需的。尽管TNF-α刺激后ICAM-1高水平表达，但ICAM-1要么无功能，要么与β2整合素的其他内皮配体冗余。
