PMID- 21208279 OWN - NLM STAT- MEDLINE DCOM- 20110202 LR - 20191210 IS - 1600-0463 (Electronic) IS - 0903-4641 (Linking) VI - 119 IP - 2 DP - 2011 Feb TI - C3b-induced eosinophil degranulation involves PI3-kinases and is inhibited by protein kinase C activity. PG - 119-26 LID - 10.1111/j.1600-0463.2010.02701.x [doi] AB - 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, GO6976 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), GO6976 (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. CI - (c) 2010 The Authors. APMIS (c) 2010 APMIS. FAU - Carlson, Marie AU - Carlson M AD - Department of Medical Sciences, University Hospital, Uppsala University, Sweden. marie.carlson@akademiska.se FAU - Venge, Per AU - Venge P FAU - Lampinen, Maria AU - Lampinen M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101201 PL - Denmark TA - APMIS JT - APMIS : acta pathologica, microbiologica, et immunologica Scandinavica JID - 8803400 RN - 0 (Carbazoles) RN - 0 (Flavonoids) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Protein Kinase Inhibitors) RN - 136194-77-9 (Go 6976) RN - 80295-43-8 (Complement C3b) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - H88EPA0A3N (Staurosporine) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Carbazoles/pharmacology MH - *Cell Degranulation MH - Complement C3b/*physiology MH - Eosinophils/*physiology MH - Extracellular Signal-Regulated MAP Kinases/physiology MH - Flavonoids/pharmacology MH - Humans MH - Phosphatidylinositol 3-Kinases/*physiology MH - Phosphoinositide-3 Kinase Inhibitors MH - Protein Kinase C/*physiology MH - Protein Kinase Inhibitors/pharmacology MH - Staurosporine/pharmacology EDAT- 2011/01/07 06:00 MHDA- 2011/02/03 06:00 CRDT- 2011/01/07 06:00 PHST- 2011/01/07 06:00 [entrez] PHST- 2011/01/07 06:00 [pubmed] PHST- 2011/02/03 06:00 [medline] AID - 10.1111/j.1600-0463.2010.02701.x [doi] PST - ppublish SO - APMIS. 2011 Feb;119(2):119-26. doi: 10.1111/j.1600-0463.2010.02701.x. Epub 2010 Dec 1.