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

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.