Rott L S, Briskin M J, Andrew D P, Berg E L, Butcher E C
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University, CA 94305.
J Immunol. 1996 May 15;156(10):3727-36.
The leukocyte integrin alpha 4 beta 7 is a receptor for the vascular mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Most circulating B and T lymphocytes in man are alpha 4+, and on these cells the regulated display of the beta 7 integrin chain determines the expression of alpha 4 beta 7 and, in large part, binding to MAdCAM-1. Among CD4+ T cells, beta 7 high memory cells (including the L-selectin+ subset) bind MAdCAM-1 better than beta 7int naive cells; whereas beta 7- memory cells,including skin homing lymphocytes, interact poorly if at all. Circulating alpha E beta 7+ T cells are alpha 4 beta 7high and also bind MAdCAM-1 well. B cells are also subdivided by beta 7 expression, and beta 7+ B cells bind MAdCAM-1 better than the beta 7low/- subset. The related vascular ligand vascular cell adhesion molecule-1 (VCAM-1), expressed on endothelium primarily in nonmucosal sites of inflammation, interacts with blood lymphocytes (including beta 7high T cells) almost exclusively via alpha 4 beta 1 and binds beta 7low/-(beta 1high) better than beta 7+ B cells and memory cells better than naive CD4+ cells. beta 7-(beta 1high) memory T cells are somewhat enriched over beta 7high memory cells at low (but not at high) VCAM-1 densities. Interestingly, CD56+ NK cells, which express both alpha 4 beta 7 and alpha 4 beta 1, bind well to VCAM-1 but poorly to MAdCAM-1. The findings indicate that the display and function of alpha 4 beta 7 determine integrin-dependent blood lymphocyte interactions with MAdCAM-1, thus delineating discrete mucosal vs nonmucosal lymphocyte populations in vivo; that alpha 4 beta 1 dominates blood lymphocyte interactions with VCAM-1; and that quantitative and qualitative regulation of MAdCAM-1 vs VCAM-1 can critically control the recruitment of specialized lymphocyte subsets during inflammation.
白细胞整合素α4β7是血管黏膜定居素细胞黏附分子-1（MAdCAM-1）的受体。人类大多数循环B淋巴细胞和T淋巴细胞为α4阳性，在这些细胞上，β7整合素链的调控性表达决定了α4β7的表达，并且在很大程度上决定了与MAdCAM-1的结合。在CD4+T细胞中，β7高表达的记忆细胞（包括L-选择素阳性亚群）比β7低表达的初始细胞与MAdCAM-1结合得更好；而β7低表达的记忆细胞，包括归巢至皮肤的淋巴细胞，即使有相互作用也很微弱。循环中的αEβ7+T细胞α4β7高表达，也能很好地结合MAdCAM-1。B细胞也根据β7表达进行细分，β7阳性B细胞比β7低表达/阴性亚群与MAdCAM-1结合得更好。相关的血管配体血管细胞黏附分子-1（VCAM-1）主要在内皮细胞的非黏膜炎症部位表达，它几乎仅通过α4β1与血液淋巴细胞（包括β7高表达的T细胞）相互作用，并且与β7低表达/阴性（β1高表达）细胞的结合优于β7阳性B细胞，与记忆细胞的结合优于初始CD4+细胞。在低（而非高）VCAM-1密度下，β7低表达（β1高表达）的记忆T细胞比β7高表达的记忆细胞略为富集。有趣的是，同时表达α4β7和α4β1的CD56+自然杀伤细胞与VCAM-1结合良好，但与MAdCAM-1结合较差。这些发现表明，α4β7的表达和功能决定了整合素依赖性血液淋巴细胞与MAdCAM-1的相互作用，从而在体内区分出离散的黏膜和非黏膜淋巴细胞群体；α4β1主导血液淋巴细胞与VCAM-1的相互作用；并且MAdCAM-1与VCAM-1在数量和质量上的调控能够在炎症过程中严格控制特定淋巴细胞亚群的募集。
