Characteristics of 1-O-hexadecyl- and 1-O-octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine-stimulated granule enzyme release from human neutrophils.
1-O-Hexadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (C16-AGEPC) and 1-O-octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (C18-AGEPC) stimulated a time- and concentration-dependent release of granule-associated lysozyme and beta-glucuronidase from human neutrophils. Maximum discharge of granule enzymes occurred between 30 and 60 sec after neutrophil exposure to C16- or C18-AGEPC (0.01-10 microM). Less than 10% of total enzyme activity is released when cells are not preincubated with cytochalasin B prior to interaction with the AGEPC analogs. A time-dependent desensitization for granule exocytosis was observed in neutrophils which were stimulated with C18-AGEPC prior to contact with cytochalasin B. The rate and amount of enzyme released by C16- and C18-AGEPC activated neutrophils was significantly enhanced in the presence of extracellular calcium. Trifluoperazine, an inhibitor of calmodulin, caused a dose-related suppression of C18-AGEPC-induced degranulation. Granule enzyme extrusion from C18-AGEPC-treated neutrophils was inhibited by the sulfhydryl reagents, N-ethylmaleimide and iodoacetic acid, and by the glycolytic inhibitor, 2-deoxy-D-glucose. Sodium cyanide was inactive. Pretreatment of neutrophils with C16- or C18-AGEPC rendered the cells unresponsive to subsequent exposure to either AGEPC analog. C18-AGEPC-induced desensitization of neutrophil degranulation appears to be stimulus specific in that serum-treated zymosan and N-formyl-methionyl-leucyl-phenylalanine were capable of eliciting granule enzyme release from C18-AGEPC-pretreated cells.
D002118:Calcium / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000201:enzymology*; D003847:Deoxyglucose / Q000494:pharmacology; D003888:Desensitization, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D009113:Muramidase / Q000097:blood*; D009504:Neutrophils / Q000201:enzymology*; D010972:Platelet Activating Factor / Q000502:physiology*; D013997:Time Factors; D014268:Trifluoperazine / Q000494:pharmacology
D010972:Platelet Activating Factor; D014268:Trifluoperazine; D003571:Cytochalasin B; D003847:Deoxyglucose; D009113:Muramidase; D002118:Calcium