Cross talk between αvβ3 and α4β1 integrins regulates lymphocyte migration on vascular cell adhesion molecule 1
Cross talk between αvβ3 and α4β1 integrins regulates lymphocyte migration on vascular cell adhesion molecule 1
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DOI：
10.1002/eji.1830271223
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发表时间：
1997-12-01
影响因子：
5.4
通讯作者：
Gisler, R
中科院分区：
文献类型：
--
作者：
Imhof, BA;Weerasinghe, D;Gisler, R
局部炎症导致血管内皮上血管细胞粘附分子（VCAM）-1的表达增加，其有助于通过白细胞配体α 4 β 1整联蛋白从循环血液中获得白细胞。炎症性血管内皮细胞高密度表达VCAM-1。我们发现，活化淋巴细胞的运动速度沿着表面迁移，与炎症内皮细胞上发现的密度相当的重组VCAM-1包被。然而，淋巴细胞在炎症条件下确实迅速迁移和外渗，这表明一定存在调节体内α 4 β 1和VCAM-1之间相互作用的机制。在这里，我们表明，淋巴细胞α v β 3整合素和整合素相关蛋白（IAP）能够调节这种相互作用。血小板细胞粘附分子-1或玻连蛋白对淋巴细胞α v β 3整合素的占据调节了重组VCAM-1上淋巴细胞α 4 β 1整合素依赖性运动的速度。这使得淋巴细胞在VCAM-1密度下快速迁移，这是典型的炎症血管。这种α v β 3介导的通过α 4 β 1增强的淋巴细胞迁移可能依赖于α v β 3整联蛋白与IAP的相互作用。此外，这种运动过程与淋巴细胞中肌动蛋白细胞骨架的极化相关。我们的研究结果表明，α v β 3整合素和α 4 β 1整合素之间的串扰是淋巴细胞运动的调节机制沿着炎症内皮细胞和随后的跨内皮迁移。这可以解释淋巴细胞如何克服与血管内皮的紧密粘附，并开始沿着并穿过血管的内皮衬里快速迁移到炎症组织中。
Local inflammation leads to increased expression of the vascular cell adhesion molecule (VCAM)-1 on vascular endothelium which contributes to the encapture of leukocytes from the circulating blood through the leukocyte ligand alpha 4 beta 1 integrin. Inflammatory vascular endothelium expresses VCAM-1 at high density. We found that the speed of locomotion of activated lymphocytes migrating along surfaces coated with recombinant VCAM-1 at a comparable density to that found on inflammatory endothelium was slow. However, lymphocytes do migrate and extravasate rapidly under inflammatory conditions, indicating that there must be mechanisms that regulate the interaction between alpha 4 beta 1 and VCAM-1 in vivo. Here we show that the lymphocyte alpha v beta 3 integrin and integrin-associated protein (IAP) is able to regulate this interaction. The occupancy of lymphocyte alpha v beta 3 integrin by platelet cell adhesion molecule-1 or vitronectin regulated the speed of alpha 4 beta 1 integrin-dependent locomotion of lymphocytes on recombinant VCAM-1. This allowed rapid lymphocyte migration at VCAM-1 densities which are typical of inflammatory vessels. This alpha v beta 3-mediated enhanced migration of lymphocytes via alpha 4 beta 1 is likely to depend on the interaction of alpha v beta 3 integrin with the IAP. Furthermore, this motile process correlates with polarization of the actin cytoskeleton in lymphocytes. Our results suggest that cross talk between alpha v beta 3 integrin and alpha 4 beta 1 integrin is a mechanism in the regulation of lymphocyte locomotion along inflammatory endothelium and subsequent transendothelial migration. This can explain how lymphocytes overcome tight adhesion to the vascular endothelium and start rapid migration along and through the endothelial lining of blood vessels into inflammatory tissue.