Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh
Correspondence: Samuel L. Jones, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough St., Raleigh, NC 27606. E-mail: sam_jones{at}ncsu.edu
The adhesive phenotype of neutrophils (PMN) depends largely on activating and deactivating intracellular signals regulating ß2 integrin avidity for ligand. Our hypothesis is that PKA is a negative regulator of ß2 integrin avidity. In this work, we examined the role of PKA in PMN 
Mß2 integrin activation. Elevation of cAMP inhibited Mß2 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 Mß2 integrin-dependent adhesion and increase ß2 integrin expression and binding of the monoclonal antibody CBRM1/5, which recognizes activated Mß2 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 ß2 integrin expression or CBRM1/5 binding. These data demonstrate that PKA appears to have a dual role in the mechanism regulating Mß2 integrin avidity and adhesion.
Key Words: immune complexes • PMN • Mß2
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