RECOGNITION OF E-CADHERIN ON EPITHELIAL-CELLS BY THE MUCOSAL T-CELL INTEGRIN ALPHA(M290)BETA-7 (ALPHA-E-BETA-7)
RECOGNITION OF E-CADHERIN ON EPITHELIAL-CELLS BY THE MUCOSAL T-CELL INTEGRIN ALPHA(M290)BETA-7 (ALPHA-E-BETA-7)
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DOI：
10.1002/eji.1830250333
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发表时间：
1995-03-01
影响因子：
5.4
通讯作者：
KILSHAW, PJ
中科院分区：
文献类型：
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作者：
KARECLA, PI;BOWDEN, SJ;KILSHAW, PJ
T细胞杂交瘤MTC-1表面的整合素(M290) β 7介导这些细胞与小鼠上皮细胞系CMT93的粘附。这种相互作用严重依赖于二价阳离子的存在；Mn2+对黏附有较强的促进作用，Ca2+对黏附无效，Mg2+对黏附有中等效果。检测CMT93细胞表面分子抗体对黏附的抑制作用。一种针对E-cadherin的单克隆抗体ECCD-2具有显著的抑制活性。其他针对e -钙粘蛋白的单克隆抗体和针对其他分子的抗体没有效果。为了证明ECCD-2对α (M290) β 7介导的粘附具有特异性，我们通过LFA-1/ICAM-1途径诱导MTC-1细胞粘附CMT93。为此，用干扰素- γ和肿瘤坏死因子-ct处理上皮细胞以诱导ICAM-1表达，此外，通过在缺乏转化生长因子-的情况下培养细胞，MTC-1细胞上的α (M290) β 7被下调。在这种情况下，LFA-1抗体可抑制MTC-1细胞对CMT93的粘附，而ECCD-2则不能。用小鼠E-cadherin cDNA转染小鼠L细胞，使MTC-1细胞通过α (M290) β 7整合素与L细胞结合；这种相互作用被ECCD-2和针对整合素的阻断抗体抑制。这些数据有力地表明e -钙粘蛋白是α (M290) β 7的主要配体。
The integrin alpha(M290)beta 7 on the surface of a T cell hybridoma, MTC-1, mediated adhesion of these cells to the mouse epithelial cell line CMT93. This interaction was critically dependent on the presence of divalent cations; Mn2+ strongly promoted adhesion, Ca2+ was ineffective and Mg2+ gave intermediate results. Antibodies to molecules on the surface of CMT93 cells were tested for inhibition of adhesion. One monoclonal antibody (mAb) against E-cadherin, ECCD-2, was found to have significant inhibitory activity. Other mAb to E-cadherin and antibodies to other molecules had no effect. To show that inhibition by ECCD-2 was specific for adhesion mediated by alpha(M290)beta 7, MTC-1 cells were induced to adhere to CMT93 via the LFA-1/ICAM-1 pathway. For this purpose, the epithelial cells were treated with interferon-gamma and tumor necrosis factor-ct to induce ICAM-1 expression and, in addition, alpha(M290)beta 7 on MTC-1 cells was down-regulated by culturing the cells in the absence of transforming growth factor beta. Under these circumstances adhesion of MTC-1 cells to CMT93 was inhibited by an antibody to LFA-1 but not by ECCD-2. Transfection of mouse L cells with cDNA for mouse E-cadherin enabled MTC-1 cells to adhere to them through the alpha(M290)beta 7 integrin; this interaction was inhibited both by ECCD-2 and by blocking antibody against the integrin. These data strongly suggest that E-cadherin is a principal ligand for alpha(M290)beta 7.