Berlin C, Bargatze R F, Campbell J J, von Andrian U H, Szabo M C, Hasslen S R, Nelson R D, Berg E L, Erlandsen S L, Butcher E C
Department of Pathology, Stanford University, California 94305.
Cell. 1995 Feb 10;80(3):413-22. doi: 10.1016/0092-8674(95)90491-3.
Of the several families of adhesion receptors involved in leukocyte-endothelial cell interactions, only the selectins have been shown to initiate leukocyte interaction under physiologic shear; indeed, beta 2 (CD18) intergrins responsible for neutrophil arrest are unable to engage without prior selectin-mediated rolling. In contrast, alpha 4 (CD49d) integrins are shown here to initiate lymphocyte contract ("tethering") in vitro under shear and in the absence of a selectin contribution. The alpha 4 integrin ligands MAdCAM-1 and VCAM-1 support loose reversible interactions including rolling, as well as rapid sticking and arrest that is favored following integrin activation. Moreover, alpha 4 beta 7 mediates L-selectin (CD62L)-independent attachment of blood-borne lymphocytes to lamina propria venules in situ. Scanning electron microscopy of alpha 4 beta 7hi lymphoid cells reveals that, like L-selectin, alpha 4 beta 7 is highly concentrated on microvillous sites of initial cellular contact, whereas the beta 2 integrin LFA-1 is excluded from villi. Thus, alpha 4 but not beta 2 integrins can initiate leukocyte adhesion under flow, a capacity that may be in part a function of topographic presentation on microvilli.
在参与白细胞与内皮细胞相互作用的几类黏附受体家族中，只有选择素已被证明在生理剪切力作用下能启动白细胞相互作用；实际上，负责中性粒细胞停滞的β2（CD18）整合素在没有先前选择素介导的滚动的情况下无法发挥作用。相比之下，α4（CD49d）整合素在此处显示在体外剪切力作用下且在没有选择素参与的情况下能启动淋巴细胞的黏附（“系留”）。α4整合素配体黏膜地址素细胞黏附分子-1（MAdCAM-1）和血管细胞黏附分子-1（VCAM-1）支持包括滚动在内的松散可逆相互作用，以及整合素激活后更易发生的快速黏附和停滞。此外，α4β7介导血源性淋巴细胞在原位与固有层小静脉的L-选择素（CD62L）非依赖性附着。对α4β7高表达的淋巴细胞进行扫描电子显微镜观察发现，与L-选择素一样，α4β7高度集中在细胞最初接触的微绒毛部位，而β2整合素淋巴细胞功能相关抗原-1（LFA-1）则被排除在微绒毛之外。因此，α4整合素而非β2整合素能在血流状态下启动白细胞黏附，这种能力可能部分是微绒毛上拓扑结构呈现的一种功能。
