Vazeux R, Hoffman P A, Tomita J K, Dickinson E S, Jasman R L, St John T, Gallatin W M
ICOS Corporation, Bothell, Washington 98021.
Nature. 1992 Dec 3;360(6403):485-8. doi: 10.1038/360485a0.
The human intercellular adhesion molecules ICAM-1, ICAM-2 and their counter-receptors, the beta 2 or leukointegrins, mediate a variety of homotypic and heterotypic leukocyte and endothelial cell-cell adhesions central to immunocompetence. It has been found that cell-cell adhesion which is dependent on expression of the leukocyte function-associated antigen LFA-1 is not always blocked completely by antibodies raised against ICAM-1 and ICAM-2. Other leukointegrin ligands therefore probably exist, such as a glycoprotein of M(r) 124K that binds LFA-1 and has been designated ICAM-3 on the basis of this function. We have molecularly cloned a new member of the ICAM family, ICAM-R, which is related to ICAM-1 and ICAM-2. The complementary DNA encoding ICAM-R is 1,781 base pairs long and the protein has five extracellular immunoglobulin-family type domains. The mature cell-surface form of the ICAM-R protein has an M(r) which varies from 116 to 140K in a cell type-specific fashion. Overall identities in protein sequence with ICAM-1 and ICAM-2 are 48% and 31% respectively, with the degree of similarity varying between individual domains. The high level of expression of ICAM-R on resting leukocytes of all lineages and its lack of expression on either resting or cytokine-activated endothelial cells indicates a pattern of expression distinct from ICAM-1 and ICAM-2. In common with ICAM-1 and ICAM-2, ICAM-R is a ligand for the beta 2-integrin CD11a/LFA-1 (CD18).
人类细胞间黏附分子ICAM - 1、ICAM - 2及其反受体β2整合素(白细胞整合素)介导了多种同型和异型白细胞与内皮细胞间的黏附,这些黏附对于免疫能力至关重要。现已发现,依赖白细胞功能相关抗原LFA - 1表达的细胞间黏附并不总是被针对ICAM - 1和ICAM - 2产生的抗体完全阻断。因此可能存在其他白细胞整合素配体,比如一种相对分子质量为124K的糖蛋白,它能结合LFA - 1,并基于此功能被命名为ICAM - 3。我们通过分子克隆得到了ICAM家族的一个新成员ICAM - R,它与ICAM - 1和ICAM - 2相关。编码ICAM - R的互补DNA长1781个碱基对,该蛋白有五个细胞外免疫球蛋白家族类型的结构域。ICAM - R蛋白成熟的细胞表面形式的相对分子质量在不同细胞类型中以特定方式在116至140K之间变化。其蛋白质序列与ICAM - 1和ICAM - 2的总体一致性分别为48%和31%,各个结构域之间的相似程度有所不同。ICAM - R在所有谱系的静息白细胞上高水平表达,而在静息或细胞因子激活的内皮细胞上均不表达,这表明其表达模式与ICAM - 1和ICAM - 2不同。与ICAM - 1和ICAM - 2一样,ICAM - R是β2整合素CD11a/LFA - 1(CD18)的配体。