DISTINCT DIVALENT-CATION REQUIREMENTS FOR INTEGRIN-MEDIATED CD4-LYMPHOCYTE ADHESION TO ICAM-1, FIBRONECTIN, VCAM-1, AND INVASIN( T)

Integrins are a large family of cell surface receptors that mediate th e adhesion of cells to other cells and to components of the extracellu lar matrix. Various divalent cations, particularly Ca2+ and Mn2+, have been shown to modulate the functional activity of many different inte grins expressed on a wide variety of cell types. In this study, we hav e characterized the divalent cation requirements for the adhesion of h uman peripheral CD4+ T cells to four distinct integrin ligands: the al pha4beta1 and alpha5beta1 ligand fibronectin, the alpha4beta1 ligand V CAM-1, the LFA-1 ligand ICAM-1, and the alpha4beta1 bacterial ligand i nvasin. We find that there are distinct divalent cation requirements o r T cell adhesion to each of these ligands: 1) Mg2+/EGTA treatment sel ectively up-regulates T cell adhesion to ICAM-1; 2) Mn2+ coordinately up-regulates adhesion to ICAM-1, fibronectin, and VCAM-1, with a peak response at 100 muM Mn2+; 3) Ca2+ can selectively support adhesion to VCAM-1 induced by activation and inhibit Mn2+-dependent adhesion to IC AM-1; and 4) binding to invasin is maximal in the presence of Ca2+, Mg 2+, or Mn2+. Furthermore, divalent cation modifications do not fully u p-regulate T cell adhesion to fibronectin, VCAM-1, and ICAM-1, because additional cell activation with phorbol ester treatment can further e nhance adhesion in the presence of Mn2+. These results suggest that mo dification of divalent cations may provide a mechanism by which an ind ividual integrin receptor/ligand interaction can be specifically and s electively regulated.