title: Differential actions of diacyl- and alkylacylglycerols in priming phospholipase A2, 5-lipoxygenase and acetyltransferase activation in human neutrophils.
abstract: One aspect of human neutrophil (PMN) function during inflammation is formation of platelet-activating factor (PAF), leukotriene B4 (LTB4), and 5-hydroxyeicosatetraenoic acid (5-HETE), but production of these lipid mediators is limited if PMN are directly stimulated with soluble, physiologic agonists. In vitro, PMN activities can be enhanced by the process of primed-stimulation where cells are sequentially treated with non-stimulatory concentrations of different agonists. Many agents that prime PMN also induce production of 1,2-diacyl- and 1-O-alkyl-2-acylglycerols. Therefore, we investigated whether diglycerides were involved in priming PMN for production of lipid mediators. We previously described the ability of the diacylglycerol, 1-oleoyl-2-acetylglycerol (OAG), and its alkylacylglycerol analog, 1-O-octadecenyl-2-acetylglycerol (EAG), to prime phospholipase A2 (PLA2) for subsequent activation by a second stimulus. However, while OAG also primed 5-lipoxygenase activity (LTB4 and 5-HETE production), EAG priming inhibited LTB4 and 5-HETE formation. We now report the effects of diglyceride priming on acetyltransferase activation (PAF formation). PMN, prelabeled with 1-O-[9',10'-3H]hexadecyl-2-lyso-sn-glycero-3-phosphocholine, were primed with OAG or EAG before stimulation. Neither OAG nor EAG induced formation of labeled PAF. Treatment of PMN with the chemotactic peptide, N-formyl-met-leu-phe (FMLP), induced low but significant production of PAF; PAF formation doubled in PMN primed with 20 microM OAG before FMLP stimulation while priming with 20 microM EAG more than tripled the level of PAF. Calcium ionophore strongly induced PAF formation; OAG priming before ionophore challenge had no effect but EAG priming further enhanced PAF formation. These results suggests a role for alkylacylglycerols in modulating the production of lipid mediators of inflammation.
authors.affiliation: Department of Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27103.
authors.forename: S A
authors.initials: SA
authors.lastname: Bauldry
authors.forename: R L
authors.initials: RL
authors.lastname: Wykle
authors.forename: D A
authors.initials: DA
authors.lastname: Bass
mesh_terms: D000123:Acetyltransferases / Q000097:blood*; D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000097:blood*; D000001:Calcimycin / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008055:Lipids / Q000097:blood* / Q000302:isolation & purification; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology*; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D010743:Phospholipids / Q000097:blood* / Q000302:isolation & purification; D010972:Platelet Activating Factor / Q000096:biosynthesis; D013329:Structure-Activity Relationship
chemical_list: D004075:Diglycerides; D008055:Lipids; D010743:Phospholipids; D010972:Platelet Activating Factor; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C038237:1-oleoyl-2-acetylglycerol; D001094:Arachidonate 5-Lipoxygenase; D000123:Acetyltransferases; D010741:Phospholipases A; D054467:Phospholipases A2