CONTROL OF LEUKOCYTE INTEGRIN ACTIVATION

The integrin receptors on leukocytes are transiently activated by ''tr iggering'' molecules that may be other leukocyte membrane structures s uch as the T-cell receptor complex or small molecules such as PAF, whi ch bind to their own specific receptors. This ''inside out'' signaling is essential for high affinity integrin/ligand pairing. In the exampl e of LFA-1/ICAM-1, binding is positively supported by Mg2+ but negativ ely supported by Ca2+. How specific divalent cations affect receptor a ctivation and subsequent ligand binding has still to be fully understo od. However, the fact that activation can be mimicked from outside the cell via special anti-LFA-l monoclonal antibodies such as MEM-83 sugg ests that activated integrins undergo conformational changes. Further alteration occurs as a result of the interaction of integrin with liga nd, and the resulting novel epitopes are named ''ligand-induced bindin g sites.'' For a brief period of time the integrin/ligand complex is a ble to transmit signals from ''outside in.'' The transient activation of leukocyte integrins determines that cell-cell adhesion will be shor t lived and serves the purpose of permitting recycling of effector cel ls with their targets.