PMID:1346139
| Citation |
Dransfield, I, Cabañas, C, Craig, A and Hogg, N (1992) Divalent cation regulation of the function of the leukocyte integrin LFA-1. J. Cell Biol. 116:219-26 |
|---|---|
| Abstract |
The integrin lymphocyte function-associated antigen-1 (LFA-1) expressed on T cells serves as a useful model for analysis of leukocyte integrin functional activity. We have assessed the role of divalent cations Mg2+, Ca2+, and Mn2+ in LFA-1 binding to ligand intercellular adhesion molecule-1 (ICAM-1) and induction of the divalent cation-dependent epitope recognized by mAb 24. Manganese strongly promoted both expression of the 24 epitope and T cell binding to ICAM-1 via LFA-1, suggesting that Mn2+ is able to directly alter the conformation of LFA-1 in a manner that favors ligand binding. Since Mn2+ also promotes functional activity of other integrins, parallels in mechanism of ligand binding may span the integrin family. In contrast, induction of 24 epitope expression by Mg2+ required removal of Ca2+ from T cell LFA-1 with EGTA. Furthermore, binding of mAb 24 to T cell LFA-1 in the presence of either Mn2+ or Mg2+ was found to be specifically inhibited by Ca2+, suggestive of a negative regulatory role for Ca2+ in the control of leukocyte integrin function. Analysis of T cell binding to ICAM-1 via LFA-1 in the presence of Mg2+ or Mn2+, confirmed that Ca2+ exerted inhibitory effects upon LFA-1 function. The implication of our findings is that Ca2+ bound with relatively high affinity to LFA-1 may serve to maintain an inactive state. Thus induction of function and 24 epitope expression may occur as a result of displacement of Ca2+ from leukocyte integrins or alternatively, such activators may be able to impose the required conformational change in the presence of bound Ca2+. |
| Links | |
| Keywords |
Animals; Antibodies, Monoclonal; Calcium/pharmacology; Cations, Divalent; Cell Adhesion Molecules/genetics; Cell Adhesion Molecules/physiology; Cells, Cultured; Edetic Acid/pharmacology; Flow Cytometry; Humans; Intercellular Adhesion Molecule-1; Kinetics; L Cells (Cell Line); Lymphocyte Function-Associated Antigen-1/drug effects; Lymphocyte Function-Associated Antigen-1/physiology; Magnesium/pharmacology; Manganese/pharmacology; Mice; Phorbol 12,13-Dibutyrate/pharmacology; T-Lymphocytes/immunology; Transfection |
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