title: Control of leukocyte integrin activation.
abstract: The integrin receptors on leukocytes are transiently activated by "triggering" molecules that may be other leukocyte membrane structures such as the T-cell receptor complex or small molecules such as PAF, which bind to their own specific receptors. This "inside out" signaling is essential for high affinity integrin/ligand pairing. In the example of LFA-1/ICAM-1, binding is positively supported by Mg2+ but negatively supported by Ca2+. How specific divalent cations affect receptor activation and subsequent ligand binding has still to be fully understood. However, the fact that activation can be mimicked from outside the cell via special anti-LFA-1 monoclonal antibodies such as MEM-83 suggests that activated integrins undergo conformational changes. Further alteration occurs as a result of the interaction of integrin with ligand, and the resulting novel epitopes are named "ligand-induced binding sites." For a brief period of time the integrin/ligand complex is able to transmit signals from "outside in." The transient activation of leukocyte integrins determines that cell-cell adhesion will be short lived and serves the purpose of permitting recycling of effector cells with their targets.
authors.affiliation: Macrophage Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
authors.forename: N
authors.initials: N
authors.lastname: Hogg
authors.forename: J
authors.initials: J
authors.lastname: Harvey
authors.forename: C
authors.initials: C
authors.lastname: Cabanas
authors.forename: R C
authors.initials: RC
authors.lastname: Landis
mesh_terms: D000818:Animals; D001666:Binding Sites, Antibody / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D006801:Humans; D016023:Integrins / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1; D007962:Leukocytes / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D015815:Cell Adhesion Molecules; D016023:Integrins; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1