ICAM-2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity

Cell adhesion mediated by the CD11/CD18 integrins and their ligands, the IC AMs, is required for many leukocyte functions. In resting cells the integri ns are nonadhesive, but when activated they become adhesive for their ligan ds, Previous findings have shown that a peptide derived from the first Ig d omain of ICAM-2 (P1) binds to LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) and activates leukocyte aggregation, Because its mechanism of action has remai ned poorly understood, we have now studied the peptide-induced ligand bindi ng in detail. Here we show that P1 was able to induce CD11/CD18-dependent a dhesion of human T lymphocytes to immobilized, purified ICAM-1, -2, and -3, The optimal peptide concentration was 150 mu g/ml, whereas concentrations higher than 400 mu g/ml did not have any stimulatory effect. The increase i n adhesion was detectable within 10 min of treatment with the peptide; it w as dependent on energy, divalent cations, temperature, and an intact cytosk eleton but was unaffected by protein kinase C and protein tyrosine kinase i nhibitors. Peptide treatment resulted in strong stimulation of the binding of soluble, recombinant ICAMs to T lymphocytes, showing that the integrin a ffinity toward its ligands was increased, Importantly, soluble ICAM-2Fc was also able to induce T lymphocyte adhesion to purified ICAM-1, -2, and -3, and it was a more potent stimulatory molecule than ICAM-1Fc or ICAM-3Fc.