ICAM-2 and a Peptide from Its Binding Domain Are Efficient Activators of Leukocyte Adhesion and Integrin Affinity

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