title: Protein kinase A regulates beta2 integrin avidity in neutrophils.
abstract: The adhesive phenotype of neutrophils (PMN) depends largely on activating and deactivating intracellular signals regulating beta2 integrin avidity for ligand. Our hypothesis is that PKA is a negative regulator of beta2 integrin avidity. In this work, we examined the role of PKA in PMN alphaMbeta2 integrin activation. Elevation of cAMP inhibited alphaMbeta2 integrin-dependent adhesion of PMN to immune complexes (IC), but not PMA-induced adhesion. The PKA inhibitor KT5720 reversed the ability of cAMP to suppress adhesion to IC. Moreover, inhibition of PKA activity was sufficient to activate alphaMbeta2 integrin-dependent adhesion and increase beta2 integrin expression and binding of the monoclonal antibody CBRM1/5, which recognizes activated alphaMbeta2 specifically. However, PKA activity was necessary for sustained adhesion. Disruption of A kinase-anchoring, protein-PKA binding with a cell-permeant peptide derived from the AKAP Ht31 also activated adhesion. Unlike pharmacologic inhibition of PKA, AKAP peptide-induced adhesion was PKC dependent and did not affect beta2 integrin expression or CBRM1/5 binding. These data demonstrate that PKA appears to have a dual role in the mechanism regulating alphaMbeta2 integrin avidity and adhesion.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. sam_jones@ncsu.edu
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Jones
mesh_terms: D018821:CD18 Antigens / Q000097:blood*; D002227:Carbazoles; D002448:Cell Adhesion; D000242:Cyclic AMP / Q000097:blood; D017868:Cyclic AMP-Dependent Protein Kinases / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction; D013449:Sulfonamides
chemical_list: D018821:CD18 Antigens; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D008024:Ligands; D011758:Pyrroles; D013449:Sulfonamides; C057416:KT 5720; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide