Distinct divalent cation requirements for integrin-mediated CD4+ T lymphocyte adhesion to ICAM-1, fibronectin,...

Integrins are a large family of cell surface receptors that mediate the adhesion of cells to other cells and to components of the extracellular matrix. Various divalent cations, particularly Ca2+ and Mn2+, have been shown to modulate the functional activity of many different integrins expressed on a wide variety of cell types. In this study, we have characterized the divalent cation requirements for the adhesion of human peripheral CD4+ T cells to four distinct integrin ligands: the alpha 4 beta 1 and alpha 5 beta 1 ligand fibronectin, the alpha 4 beta 1 ligand VCAM-1, the LFA-1 ligand ICAM-1, and the alpha 4 beta 1 bacterial ligand invasin. We find that there are distinct divalent cation requirements for T cell adhesion to each of these ligands: 1) Mg2+/EGTA treatment selectively 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 microM Mn2+; 3) Ca2+ can selectively support adhesion to VCAM-1 induced by activation and inhibit Mn(2+)-dependent adhesion to ICAM-1; and 4) binding to invasin is maximal in the presence of Ca2+, Mg2+, or Mn2+. Furthermore, divalent cation modifications do not fully up-regulate T cell adhesion to fibronectin, VCAM-1, and ICAM-1, because additional cell activation with phorbol ester treatment can further enhance adhesion in the presence of Mn2+. These results suggest that modification of divalent cations may provide a mechanism by which an individual integrin receptor/ligand interaction can be specifically and selectively regulated.