alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow

Cell. 1995 Feb 10;80(3):413-22. doi: 10.1016/0092-8674(95)90491-3.


Of the several families of adhesion receptors involved in leukocyte-endothelial cell interactions, only the selectins have been shown to initiate leukocyte interaction under physiologic shear; indeed, beta 2 (CD18) intergrins 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 contract ("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 7hi 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.

Publication types

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

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Cell Communication
  • Cell Movement
  • Immunoglobulins / metabolism
  • Integrin alpha4
  • Integrin beta Chains*
  • Integrins / analysis
  • Integrins / metabolism
  • Integrins / physiology*
  • Intestine, Small / blood supply
  • Lymphocyte Activation
  • Lymphocyte Function-Associated Antigen-1 / analysis
  • Lymphocytes / cytology*
  • Lymphocytes / ultrastructure
  • Mice
  • Microvilli / chemistry
  • Mucoproteins / metabolism
  • Tumor Cells, Cultured
  • Vascular Cell Adhesion Molecule-1
  • Venules / metabolism


  • Cell Adhesion Molecules
  • Immunoglobulins
  • Integrin beta Chains
  • Integrins
  • Lymphocyte Function-Associated Antigen-1
  • Madcam1 protein, mouse
  • Mucoproteins
  • Vascular Cell Adhesion Molecule-1
  • integrin beta7
  • Integrin alpha4