title: Beta-adrenergic stimulation suppresses phagocytosis via Epac activation in murine microglial cells.
abstract: Endogenous noradrenaline presumably prohibits neuroinflammation by stimulation of β-adrenergic receptor-dependent suppression of the production of inflammatory mediators. Using the microglial cell line, BV-2, as well as primary murine microglial cells, we show here that the β-adrenergic agonist, isoproterenol, suppresses uptake of hydrophobic polystyrene microspheres. The number of cells showing a specific number of engulfed microspheres followed a Poisson distribution. Isoproterenol decreased the number of engulfed particles per cell and the number of cells showing at least one incorporated particle. Elevation of intracellular cAMP by activation of adenylyl cyclase activity with forskolin, suppression of phosphodiesterase activity with 3-isobutyl-1-methylxanthine (IBMX), or application of the membrane-permeable cAMP analog, 8-bromo-cAMP, suppressed particle uptake. The protein kinase A inhibitor, H-89, did not prevent isoproterenol-dependent suppression of particle engulfment. However, activation of exchange protein activated by cAMP (Epac), specific guanine nucleotide exchange factors for the Ras GTPase homologues, Rap1 and Rap2, with the Epac1-specific cAMP analog, 8-pCPT-2'-O-Me-cAMP, mimicked the suppressive effect of isoproterenol on particle uptake. Our results suggest that β-adrenergic receptor stimulation suppresses particle uptake in microglia by cAMP-dependent activation of Epac.
authors.affiliation: Department of Cellular Biology, Division of Molecular and Cellular Neurobiology, University of Salzburg, Hellbrunnerstr. 34, 5020 Salzburg, Austria.
authors.forename: Tanja S
authors.initials: TS
authors.lastname: Steininger
authors.forename: Hanno
authors.initials: H
authors.lastname: Stutz
authors.forename: Hubert H
authors.initials: HH
authors.lastname: Kerschbaum
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000187:drug effects* / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009638:Norepinephrine / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011137:Polystyrenes; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical
chemical_list: D000318:Adrenergic beta-Agonists; C482601:Epac protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D011137:Polystyrenes; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine