Meyer D M, Dustin M L, Carron C P
Department of Immunology, Monsanto Company, St. Louis, MO 63198, USA.
J Immunol. 1995 Oct 1;155(7):3578-84.
Intercellular adhesion molecule-1 (ICAM-1) is a member of the Ig superfamily, contains five Ig-like domains comprising the extracellular portion of the molecule, and interacts with lymphocyte function-associated molecule-1 (LFA-1), a member of the beta 2-integrin family. LFA-1/ICAM-1 interaction is important in a variety of cellular events including Ag-specific T cell activation and leukocyte transendothelial migration. Recently, a soluble circulating form of ICAM-1 has been detected in human serum that appears to result from the proteolytic cleavage of membrane ICAM-1. Native and recombinant soluble forms of ICAM-1 have been reported to inhibit LFA-1/ICAM-mediated adhesion in vitro, and it is conceivable that circulating forms of soluble ICAM-1 are regulators of LFA-1/ICAM-1-mediated cell-cell interaction in vivo. We have investigated the properties of the ICAM-1 ectodomain (sICAM453) as an inhibitor of LFA-1 interaction with ICAM-1 in cell- and molecule-based systems. The results show clearly that recombinant sICAM453 can inhibit LFA-1/ICAM-1 interaction. Soluble ICAM-1 inhibited LFA-1-mediated cell adhesion to immobilized sICAM453 and homotypic T-cell aggregation with IC50 in the 20 to 40 microM range. Definitive evidence that sICAM-1 can inhibit LFA-1 interaction with ICAM-1 was obtained by showing that the sICAM-1 inhibited the interaction between LFA-1 protein micelles and ICAM-1 immobilized on plastic. These results clearly show that sICAM453 can bind to LFA-1 and competitively inhibit ICAM-1/LFA-1-mediated cell-cell interaction, albeit at concentrations much greater than found in plasma. As a consequence, it is unlikely that sICAM-1 would antagonize ICAM-1/LFA-1-mediated cellular events in vivo.
细胞间黏附分子-1（ICAM-1）是免疫球蛋白超家族的成员，包含五个免疫球蛋白样结构域，构成该分子的细胞外部分，并与β2整合素家族成员淋巴细胞功能相关分子-1（LFA-1）相互作用。LFA-1/ICAM-1相互作用在多种细胞事件中很重要，包括抗原特异性T细胞活化和白细胞跨内皮迁移。最近，在人血清中检测到一种可溶性循环形式的ICAM-1，它似乎是由膜ICAM-1的蛋白水解切割产生的。据报道，天然和重组可溶性形式的ICAM-1在体外可抑制LFA-1/ICAM介导的黏附，并且可以想象，可溶性ICAM-1的循环形式是体内LFA-1/ICAM-1介导的细胞间相互作用的调节因子。我们已经在基于细胞和分子的系统中研究了ICAM-1胞外域（sICAM453）作为LFA-1与ICAM-1相互作用抑制剂的特性。结果清楚地表明，重组sICAM453可以抑制LFA-1/ICAM-1相互作用。可溶性ICAM-1抑制LFA-1介导的细胞与固定化sICAM453的黏附以及同型T细胞聚集，IC50在20至40微摩尔范围内。通过证明sICAM-1抑制LFA-1蛋白微团与固定在塑料上的ICAM-1之间的相互作用，获得了sICAM-1可以抑制LFA-1与ICAM-1相互作用的确凿证据。这些结果清楚地表明，sICAM453可以与LFA-1结合并竞争性抑制ICAM-1/LFA-1介导的细胞间相互作用，尽管其浓度远高于血浆中的浓度。因此，sICAM-1不太可能在体内拮抗ICAM-1/LFA-1介导的细胞事件。
