Lymphocyte adhesion mediated by lymphocyte function-associated antigen-1. I. Long term augmentation by transient increases in intracellular cAMP.
Lymphocyte adhesion to target cells is mediated, in part, by the interaction of lymphocyte function-associated Ag-1 (LFA-1) with intercellular adhesion molecule-1 (ICAM-1). Cells of the B cell line, JY, express both coreceptors and have been used as a model for intercellular adhesion mediated by these molecules. Elevation of the intracellular cAMP concentration ([cAMP]i), by any of several reagents, for periods as brief as 30 min, led to enhanced intercellular adhesion in a concentration dependent manner 5 to 8 h later. Two protein kinase A inhibitors, KT5720 and H-89, but not the protein kinase C inhibitor calphostin C, blocked the effects of elevated [cAMP]i. These data suggest a role for protein kinase A in this response. The adhesion augmented by increased [cAMP]i was due to LFA-1/ICAM-1 interactions between cells because it was blocked by either anti-LFA-1 or anti-ICAM-1 mAb. Elevated [cAMP]i induced cell surface patching of LFA-1, but not ICAM-1, and this redistribution preceded intercellular adhesion. Finally, redistribution of LFA-1 was not mediated by the cytoskeleton. These results suggest a model in which transient activation of protein kinase A results in increased local concentration of LFA-1 at the cell surface and in augmented long term adhesion mediated by this integrin.
Haverstick
D M
DM
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
Gray
L S
LS
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002449:Cell Aggregation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D000242:Cyclic AMP; D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate