Kinetic and mechanical basis of rolling through an integrin and novel Ca2+-dependent rolling and Mg2+-dependent firm adhesion modalities for the α4β7-MAdCAM-1 interaction
Kinetic and mechanical basis of rolling through an integrin and novel Ca2+-dependent rolling and Mg2+-dependent firm adhesion modalities for the α4β7-MAdCAM-1 interaction
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DOI：
10.1021/bi011582f
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发表时间：
2001-11-20
期刊：
影响因子：
2.9
通讯作者：
Springer, TA
中科院分区：
文献类型：
--
作者：
de Château, M;Chen, SQ;Springer, TA
我们研究了在剪切流的细胞轴承整合素α 4 β 1或α 4 β 7与VCAM-1和MAdCAM-1基板在不同的二价阳离子的相互作用。有趣的是，Ca 2+是必不可少的束缚在流动和滚动，通过两个α 4整合素的相互作用。Mg 2+促进表达α 4 β 7的细胞在MAdCAM-1上的牢固粘附，但在剪切流中具有低得多的栓系效率。对于MAdCAM-1上的瞬时系链，1.28s-1的Ki，ff'和受体-配体键对力的L抗性（估计为键相互作用距离或Gr）与E-和P-选择素的值相似。与Ca 2+或Ca 2 + + Mg 2+中的结果相比，α 4 β 7-MAdCAM-1的k（off）度降低了20倍，为0.046 s（-1），并且结合较弱，这为在这些条件下发现牢固的粘附提供了解释。剪切增强了对MAdCAM-1的束缚，从而有助于滚动的稳定性。与选择素的比较表明，α 4 β 7整联蛋白的动力学和机械性质非常适合其在粘附级联中的中间位置，其中它桥接通过选择素的快速滚动以通过β 2整联蛋白的牢固粘附。
We studied interactions in shear flow of cells bearing integrins alpha4 beta1 or alpha4 beta7 with VCAM-1 and MAdCAM-1 substrates in different divalent cations. Interestingly, Ca2+ was essential for tethering in flow and rolling, interactions through both alpha4 integrins. Mg2+ promoted firm adhesion of alpha4 beta7-expressing cells on MAdCAM-l but with much lower tetherina efficiency in shear flow. The k,,ff' of 1.28 s-1 and L resistance of the receptor-ligand bond to force (estimated as a bond interaction distance or Gr) for transient tethers on MAdCAM-1 were similar to values for E- and P-selectins. By contrast to results in Ca2+ or Ca2+ + Mg2+ in Mg2+ the alpha4 beta7-MAdCAM-1 k(off)degrees decreased 20-fold to 0.046 s(-1), and the bond was weaker, providing an explanation for the finding of firm adhesion under these conditions. Shear enhanced tethering to MAdCAM-1, thereby contributing to the stability of rolling. Comparisons to selectins demonstrate that the kinetic and mechanical properties of the alpha4 beta7 integrin are well suited to its intermediate position in adhesion cascades, in which it bridges rapid rolling through selectins to firm adhesion through beta2 integrins.