ALPHA-4 INTEGRINS MEDIATE LYMPHOCYTE ATTACHMENT AND ROLLING UNDER PHYSIOLOGICAL FLOW
ALPHA-4 INTEGRINS MEDIATE LYMPHOCYTE ATTACHMENT AND ROLLING UNDER PHYSIOLOGICAL FLOW
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DOI：
10.1016/0092-8674(95)90491-3
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发表时间：
1995-02-10
期刊：
影响因子：
64.5
通讯作者：
BUTCHER, EC
中科院分区：
文献类型：
--
作者：
BERLIN, C;BARGATZE, RF;BUTCHER, EC
在参与白细胞-内皮细胞相互作用的几个黏附受体家族中，只有选择素被证明在生理剪切力下启动白细胞相互作用；事实上，负责中性粒细胞抑制的β2(CD18)整合素在没有选择素介导的滚动的情况下无法参与。相反，在没有选择素作用的情况下，阿尔法4(CD49d)整合素在体外剪切力和没有选择素作用的情况下，启动淋巴细胞接触(‘系留’)。α4整合素配体MAdCAM-1和VCAM-1支持松散的可逆相互作用，包括滚动，以及整合素激活后有利于快速粘连和停滞。此外，α4β7介导了L-选择素(CD62L)非依赖的血源性淋巴细胞与固有层小静脉的原位黏附。扫描电子显微镜显示，与L-选择素一样，α4-β7高度集中在细胞最初接触的微绒毛部位，而β2整合素LFA-1则不在绒毛中。因此，α4整合素而不是β2整合素可以在流动状态下启动白细胞黏附，这种能力可能部分是微绒毛上的地形呈现的功能。
Of the several families of adhesion receptors involved in leukocyte-endoethelial cell interactions, only the selectins have been shown to initiate leukocyte interaction under physiologic shear; indeed, beta 2 (CD18) integrins 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 contact (''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 7(hi) 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.