T-CELL ADHESION TO INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) IS CONTROLLED BY CELL SPREADING AND THE ACTIVATION OF INTEGRIN LFA-1

Many leukocyte integrins require activation before they can adhere to their ligands, For example, stimulation of T cells enables the integri n LFA-1 to bind to ligand, This study compares two well known protocol s for inducing T cell LFA-l-mediated adhesion to intercellular adhesio n molecule-1 (ICAM)-1, We show that treatment with high concentrations of the divalent cation Mg2+ induces a high affinity state of LFA-1, w hich is reflected in the binding of soluble ICAM-1 and correlates with the expression of the epitope recognized by mAb 24, The second stimul ation protocol with the phorbol ester phorbol-12,13-dibutyrate (PDBu) does not induce a high affinity state of LFA-1, and in this situation, adhesion is dependent on cell spreading and intracellular events invo lving protein kinase C, [Ca2+](i), and actin polymerization, These low affinity LFA-1 receptors are responsible for the initial contact with immobilized ligand because, unlike the Mg2+-stimulated receptors, adh esion is not blocked by soluble ICAM-1, Finally, we used a third metho d of inducing LFA-1-mediated adhesion by stimulation of T cells throug h the TCR/CD3 complex, This procedure, which is considered to be a mor e physiologic trigger for LFA-1 activation, resembles the phorbol este r protocol in that high affinity LFA-1 receptors are not induced and c ell adhesion depends on involvement of the cytoskeleton and cell sprea ding.