title: The effects of cAMP modulation upon the adhesion and respiratory burst activity of immune complex-stimulated equine neutrophils.
abstract: Toxic products such as reactive oxygen intermediates released by activated polymorphonuclear neutrophil (PMN) have an important role in the pathophysiology of diseases associated with the deposition of immune complexes (IC) in tissues. IC-induced activation of PMN requires adhesion mediated by integrin adhesion receptors. Of the integrins expressed on PMN, the beta(2) family has been found to be of particular importance for activation of PMN by IC. beta(2) Integrin ligand binding must be activated to enable adhesion to IC. Both activating and inhibitory signals regulate beta(2) integrin ligand avidity and adhesion. The second messenger cyclic adenosine monophosphate (cAMP) has been demonstrated to inhibit the activation of PMN in response to a variety of stimuli. The purpose of this study is to test the hypothesis that cAMP-dependent signals inhibit beta(2) integrin-dependent adhesion of equine PMN to immobilized IC and subsequent adhesion-dependent activation of respiratory burst activity. Treatment of equine PMN with beta(2) adrenergic agonists isoproterenol or clenbuterol, which trigger an increase in intracellular cAMP concentration, inhibited adhesion of equine PMN to IC in a dose dependent manner. Similarly, inhibition of cAMP hydrolysis by the non-specific phosphodiesterase (PDE) inhibitor pentoxifylline and the PDE 4-specific inhibitor rolipram inhibited adhesion of equine PMN to IC. Elevation of intracellular cAMP levels with pentoxifylline, clenbuterol and rolipram also inhibited IC-induced activation of respiratory burst activity in equine PMN. Importantly, co-treatment of equine PMN with rolipram and either beta(2) adrenergic agonist synergistically inhibited both the adhesion of equine PMN to IC as well as the subsequent respiratory burst activity.
authors.affiliation: Department of Clinical Sciences, North Carolina College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
authors.forename: Clayton D
authors.initials: CD
authors.lastname: Chilcoat
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Rowlingson
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Jones
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002976:Clenbuterol / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000276:immunology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000276:immunology; D006736:Horses / Q000097:blood / Q000276:immunology*; D007545:Isoproterenol / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D010431:Pentoxifylline / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D016897:Respiratory Burst / Q000276:immunology*; D020889:Rolipram / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D000936:Antigen-Antibody Complex; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020889:Rolipram; D007545:Isoproterenol; D010431:Pentoxifylline; D002976:Clenbuterol