Rolling adhesion through an extended conformation of integrin alphaLbeta2 and relation to alpha I and beta I-like domain interaction

Immunity. 2004 Apr;20(4):393-406. doi: 10.1016/s1074-7613(04)00082-2.


In vivo, beta(2) integrins and particularly alpha(L)beta(2) (LFA-1) robustly support firm adhesion of leukocytes, but can also cooperate with other molecules in supporting rolling adhesion. Strikingly, a small molecule alpha/beta I-like allosteric antagonist, XVA143, inhibits LFA-1-dependent firm adhesion, while at the same time it enhances adhesion in shear flow and rolling both in vitro and in vivo. XVA143 appears to induce the extended conformation of integrins as shown by increased activation epitope exposure. Fab to the beta(2) I-like domain converts firm adhesion to rolling adhesion, but does not enhance adhesion. Residue alpha(L)-Glu-310 in the linker following the I domain is critical for communication to the beta(2) I-like domain, rolling, integrin extension, and activation by Mn(2+) of firm adhesion. The results demonstrate the importance of integrin extension in rolling, and suggest that rolling and firm adhesion are mediated by extended conformations of alpha(L)beta(2) that differ in the affinity of the alpha(L) I domain for ICAM-1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / immunology
  • Cell Line
  • Flow Cytometry
  • Humans
  • Integrin alpha1 / chemistry
  • Integrin alpha1 / immunology*
  • Integrin beta1 / chemistry
  • Integrin beta1 / immunology*
  • Intercellular Adhesion Molecule-1 / immunology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukocyte Rolling / immunology*
  • Lymphocyte Activation / immunology
  • Lymphocyte Function-Associated Antigen-1 / chemistry
  • Lymphocyte Function-Associated Antigen-1 / immunology*
  • Mice
  • Molecular Conformation


  • Integrin alpha1
  • Integrin beta1
  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1