Regulated expression of Mg2+ binding epitope on leukocyte integrin alpha subunits.
The leukocyte integrins LFA-1, CR3 and p150,95 are a family of heterodimeric receptors that mediate divalent cation-dependent cellular adhesion reactions. In this study we describe a novel antibody-defined epitope present on the leukocyte integrin alpha subunits indicating that the antibody recognizes a structural feature common to all three polypeptides. Antibody recognition further differs from that of previously described anti-leukocyte integrin antibodies in that it is strictly dependent upon the presence of Mg2+. This suggests that the epitope is located within, or in close proximity to, the three conserved cation binding domains and is therefore a measure of Mg2+ bound to the leukocyte integrins and thus reflects functionally active molecules. The epitope can be induced on polymorphonuclear leukocytes, a subset of T cells and on monocytes but is absent or much reduced at low temperature or in the presence of metabolic inhibitors. These observations have considerable implications for the regulation of leukocyte integrin function suggesting that Mg2+ binding to the extracellular domain(s) of the alpha subunits is controlled from within the cell. We suggest that one mechanism by which ligand binding by these molecules can be 'switched' on and off in response to external signals is by regulation of Mg2+ binding to these molecules, converting from the cation-free, 'inactive' to the Mg2+-bound, 'active' form.
Dransfield
I
I
Macrophage Laboratory, Imperial Cancer Research Fund, London, UK.
Hogg
N
N
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000378:metabolism* / Q000502:physiology; D009000:Monocytes / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D016028:Receptors, Leukocyte-Adhesion; D008274:Magnesium