T cell adhesion to intercellular adhesion molecule-1 (ICAM-1) is controlled by cell spreading and the activation of integrin LFA-1.
Many leukocyte integrins require activation before they can adhere to their ligands. For example, stimulation of T cells enables the integrin LFA-1 to bind to ligand. This study compares two well known protocols for inducing T cell LFA-1 mediated adhesion to intercellular adhesion molecule-1 (ICAM)-1. We how that treatment with high concentrations of the divalent cation Mg2+ induces a high affinity state of LFA-1, which is reflected in the binding of soluble ICAM-1 and correlates with the expression of the epitope recognized by mAb 24. The second stimulation protocol with the phorbol ester phorbol-12,13-dibutyrate (PDBu) does not induce a high affinity state of LFA-1, and in this situation, adhesion is dependent on cell spreading and intracellular events involving protein kinase C, [Ca2+]i, and actin polymerization. These low affinity LFA-1 receptors are responsible for the initial contact with immobilized ligand because, unlike the Mg2+-stimulated receptors, adhesion is not blocked by soluble ICAM-1. Finally, we used a third method of inducing LFA-1-mediated adhesion by stimulation of T cells through the TCR/CD3 complex. This procedure, which is considered to be a more physiologic trigger for LFA-1 activation, resembles the phorbol ester protocol in that high affinity LFA-1 receptors are not induced and cell adhesion depends on involvement of the cytoskeleton and cell spreading.
Stewart
M P
MP
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, London, UK.
Cabanas
C
C
Hogg
N
N
D000911:Antibodies, Monoclonal / Q000737:chemistry; D001665:Binding Sites / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D008274:Magnesium