title: C3b-induced eosinophil degranulation involves PI3-kinases and is inhibited by protein kinase C activity.
abstract: Selective release of individual eosinophil granule proteins has been demonstrated in eosinophilic conditions and in vitro using different stimuli. The aim of this study was to investigate if selective release of eosinophil cationic protein (ECP), eosinophil protein X/eosinophil derived-neurotoxin (EPX/EDN) and eosinophil peroxidase (EPO) could be due to the involvement of different signal transduction pathways. Peripheral blood granulocytes from healthy donors were incubated with Wortmannin, LY294002, Genistein, Staurosporine, GÖ6976 or PD98059 prior to the induction of degranulation by C3b. The released amounts of ECP, EPO and EPX/EDN were determined by immunoassays, and related to the total cell content of respective protein. Wortmannin caused a significant, dose-dependent inhibition of all three granule proteins. LY294002 (10⁻⁶ M) also inhibited the release of all proteins. Genistein (10⁻⁶ M) inhibited the release of ECP, whereas the release of EPO was increased. However, there was a tendency towards similar concentration-dependent patterns of release of all three proteins. Staurosporine (10⁻⁷ M), GÖ6976 (10⁻⁶ M) and PD98059 (10⁻⁵ M) caused an increased release of the three proteins. PI3-kinases play an important role in the C3b-induced release of ECP, EPO and EPX/EDN, whereas protein kinase C seems to have inhibitory effects on C3b-induced degranulation.
authors.affiliation: Department of Medical Sciences, University Hospital, Uppsala University, Sweden. marie.carlson@akademiska.se
authors.forename: Marie
authors.initials: M
authors.lastname: Carlson
authors.forename: Per
authors.initials: P
authors.lastname: Venge
authors.forename: Maria
authors.initials: M
authors.lastname: Lampinen
mesh_terms: D002227:Carbazoles / Q000494:pharmacology; D015550:Cell Degranulation; D003179:Complement C3b / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D002227:Carbazoles; D003179:Complement C3b; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D019311:Staurosporine; C081021:Go 6976; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one