Biochemical signals transmitted by Fc gamma receptors: triggering mechanisms of the increased synthesis of adenosine-3',5'-cyclic monophosphate mediated by Fc gamma 2a- and Fc gamma 2b- -receptors of a murine macrophage-like cell line (P388D1).
The specific binding of IgG2a or IgG2b subclass monoclonal anti-sheep erythrocyte antibodies to P388D1 cell surface Fc gamma 2aR3 or Fc gamma 2bR, respectively, triggered the synthesis of adenosine-3'5'-monophosphate (cAMP) to an approximately same extent by the mechanisms that are apparently unique for each type of Fc gamma Rs. Fc gamma 2aR appeared to trigger directly, upon binding of IgG2a antibodies, the adenylate cyclase system without requiring the participation of guanine nucleotide-binding (G/F) regulatory protein, because the Fc gamma 2aR-triggered cAMP synthesis, which reached maximum within 30 min, was not significantly affected by an uncoupler, Mn++ or by addition of guanosine triphosphate (GTP) analog, 5'-guanylylimidodiphosphate (Gpp(NH)p). In contrast, Fc gamma 2bR appeared to stimulate indirectly the G/F regulatory requiring-adenylate cyclase system by generating prostaglandins, since the cAMP synthesis, which required 90 min to reach plateau after binding of IgG2b to Fc gamma 2bR, was totally suppressed by phospholipase A2 inhibitor (p-bromophenacylbromide) or cyclo-oxygenase inhibitor (indomethacin), partially suppressed by Mn++, and slightly increased by Gpp(NH)p. Furthermore, the inhibition of phagocytic process by cytochalasin D increased cAMP synthesis mediated by Fc gamma 2aR (about 70% at 2 micrograms/ml), but did not affect Fc gamma 2bR-mediated cAMP synthesis. In addition, our data suggested that both Fc gamma 2aR- and Fc gamma 2bR-mediated cAMP synthesis are independent from beta-adrenergic receptor-mediated stimulation of the adenylate cyclase system, since either beta-agonist (isoproterenol) or beta-antagonist (propranolol) did not affect significantly the levels of cAMP produced in response to EA-stimulation.
D000098:Acetophenones / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D003572:Cytochalasins / Q000494:pharmacology; D007142:Immunoglobulin gamma-Chains; D007545:Isoproterenol / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D011433:Propranolol / Q000494:pharmacology; D011458:Prostaglandins E / Q000276:immunology; D011961:Receptors, Fc / Q000502:physiology*; D012397:Rosette Formation
D000098:Acetophenones; D003572:Cytochalasins; D007142:Immunoglobulin gamma-Chains; D011458:Prostaglandins E; D011961:Receptors, Fc; D011433:Propranolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; C006821:4-bromophenacyl bromide