Lymphocyte adhesion mediated by lymphocyte function-associated antigen-1. II. Interaction between phorbol ester- and cAMP-sensitive pathways.
Ag independent adhesion between lymphocytes and target cells is mediated in part by the interaction between lymphocyte function associated Ag-1 (LFA-1) and its coreceptor intercellular adhesion molecule-1 (ICAM-1). Within minutes, PMA treatment of JY cells, which express both LFA-1 and ICAM-1, induced capping of LFA-1 and augmentation of intercellular adhesion lasting for several hours. However, over the course of 15 to 30 min, both of these events were blocked by elevation of intracellular cAMP concentration ([cAMP]i) presumably via activation of protein kinase A. This short term inhibition of protein kinase C-induced adhesion was in contrast to the long term augmentation of adhesion caused by increased [cAMP]i as demonstrated in the companion article. Intercellular adhesion, due to LFA-1/ICAM-1 interactions, could also be induced by LPS treatment of JY cells. At submaximal concentrations, the extent of aggregation induced by LPS had two maxima, one at 30 to 60 min and the other with a plateau at 5 to 8 h. LPS is known to activate protein kinase C and we show that LPS treatment induced increased [cAMP]i. Using inhibitors of protein kinases C and A, possible mediators of the two components of adhesion induced by LPS could be identified. The early component was abrogated by inhibition of protein kinase C although the later component was unaffected. In contrast, an inhibitor of protein kinase A had no affect on the early component and attenuated, but did not entirely eliminate, the late component. These results suggest a model of sequential induction, inhibition, and reinduction of LFA-1/ICAM-1-mediated lymphocyte adhesion that is regulated by temporally ordered actions and interactions of protein kinases C and A.
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
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Haverstick
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Gray
D002227:Carbazoles; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002449:Cell Aggregation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002227:Carbazoles; D015815:Cell Adhesion Molecules; D007211:Indoles; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D011758:Pyrroles; D018799:Intercellular Adhesion Molecule-1; C057416:KT 5720; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate