Differential actions of diacyl- and alkylacylglycerols in priming phospholipase A2, 5-lipoxygenase and acetyltransferase activation in human neutrophils

Bauldry, S A; Wykle, Robert L.; Bass, David

doi:10.1016/0005-2760(91)90218-7

Cited by 37 publications

(24 citation statements)

References 47 publications

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“…Under normal circumstances, leukocytes stimulated with receptor-mediated stimuli, including PAF and FMLP, or with submaximal concentrations of calcium ionophore generate litde or undetectable amounts of eicosanoids unless the cells are first primed (37,38). Priming is therefore a critical step in the activation of PMN during inflammation and has been the subject of several investigations.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids.

Bozza

Payne

Goulet

et al. 1996

The Journal of Experimental Medicine

147

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SummaryLipid bodies, hpid-rich cytoplasmic inclusions, are characteristically abundant in vivo in leukocytes associated with inflammation. Because lipid bodies are potential reservoirs of esterified arachidohate and sites at which eicosanoid-forming enzymes may localize, we evaluated mechanisms of lipid body formation in neutrophils (PMN). Among receptor-mediated agonists, platelet-activating factor (PAF), but not C5a, formyl-methyl-phenylalanine, interleukin 8, or leukotriene (LT) B4, induced the rapid formation of lipid bodies in PMN. This action of PAF was receptor mediated, as it was dose dependently inhibited by the PAF receptor antagonist WEB 2086 and blocked by pertussis toxin. Lipid body induction by PAF required 5-lipoxygenase (LO) activity and was inhibited by the 5-1ipoxygenase-activating protein antagonist MK 886 and the 5-LO inhibitor zileuton, but not by cyclooxygenase inhibitors. Corroborating the dependency of PAF-induced lipid body formation on 5-LO, PMN and macrophages from wild-type mice, but not from 5-LO genetically deficient mice, formed lipid bodies on exposure to PAF both in vitro and in vivo within the pleural cavity. The 5-LO product inducing lipid body formation was not LTB4 but was 5(S)-hydroxyeicosatetraenoic acid [5(S)-HETE], which was active at 10-fold lower concentrations than PAF and was also inhibited by pertussis toxin but not by zileuton or WEB 2086. Furthermore, 5-HETE was equally effective in inducing lipid body formation in both wild-type and 5-LO genetically deficient mice. Both PAF-and 5(S)-HETE-induced lipid body formation were inhibited by the protein kinase C (PKC) inhibitors staurosporine and chelerythrine, the phosphotipase C (PLC) inhibitors D609 and U-73122, and by actinomycin D and cycloheximide. Prior stimulation of human PMN with PAF to form lipid bodies enhanced eicosanoid production in response to submaximal stimulation with the calcium ionophore A23187; and the levels of both prostaglandin (PG) E 2 and LTB 4 correlated with the number of lipid bodies. Furthermore, pretreatment of cells with actinomycin D or cycloheximide inhibited not only the induction of lipid body formation by PAF, but also the PAF-induced "priming" for enhanced PGE 2 and LTB 4 in PMN. Thus, the compartmentalization of lipids to form lipid bodies in PMN is dependent on specific cellular responses that can be PAF receptor mediated, involves signaling through 5-LO to form 5-HETE and then through PKC and PLC, and requires new protein synthesis. Since increases in lipid body numbers correlated with priming for enhanced PGE 2 and LTB4 production in PMN, the induction of lipid bodies may have a role in the formation of eicosanoid mediators by leukocytes involved in inflammation.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids.

Bozza

Payne

Goulet

et al. 1996

The Journal of Experimental Medicine

147

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“…[192][193][194][195][196] Alkylglycerols have been suggested to play a role in modulating the production of lipid mediators of inflammation by priming PLA 2 , 5-lipoxygenase, and acetyltransferase activation in PMN. 197 PLA 2 in rabbit and human PMN may also contribute to the bactericidal activity of these cells by hydrolyzing PLs. [198][199][200] PLA 2 activity has been demonstrated both in human and rabbit neutrophils.…”

Section: Polymorphonuclear Leukocytesmentioning

confidence: 97%

Phospholipase A₂: Its Usefulness in Laboratory Diagnostics

Kaiser

1999

Critical Reviews in Clinical Laboratory Sciences

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Phospholipase A2 (PLA2) is an enzyme that catalyzes the hydrolysis of membrane phospholipids. This article reviews the source and structure of PLA2, the involvement of the enzyme in various biological and pathological phenomena, and the usefulness of PLA2 assays in laboratory diagnostics. Of particular importance is the role of PLA2 in the cellular production of mediators of inflammatory response to various stimuli. Assays for PLA2 activity and mass concentration are discussed, and the results of enzyme determinations in plasma from patients with different pathological conditions are presented. The determination of activity and mass concentration in plasma is particularly useful in the diagnosis and prognosis of pancreatitis, multiple organ failure, septic shock, and rheumatoid arthritis. A very important result is the demonstration that PLA2 is an acute phase protein, like CRP. Indeed, there is a close correlation between PLA2 mass concentration and CRP levels in several pathological conditions. Although the determination of C-reactive protein is much easier to perform and is routinely carried out in most clinical laboratories, the assessment of PLA2 activity or mass concentration has to be considered as a reliable approach to obtain a deeper understanding of some pathological conditions and may offer additional information concerning the prognosis of several disorders.

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“…Activation of 5-LO in the cell involves the initial conversion of the active site iron from the ferrous to the ferric state and is accompanied by a translocation process of the enzyme to the nuclear membrane, where it cofunctions with the 5-LO-activating protein (for review, see Werz, 2002). Such an initial cellular activation of 5-LO can be mediated by elevated Ca 2ϩ levels and/or 5-LO phosphorylation at serine residues by members of the mitogen-activated protein kinase (MAPK) family (Werz, 2002), as well as by DAGs, such as 1-oleoyl-2-acetylglycerol (Bauldry et al, 1991;Albert et al, 2003). In fact, several stimuli capable to induce 5-LO product synthesis, including ligands of G protein-coupled receptors (GPCRs) but also nonreceptor-coupled stimuli such as thapsigargin or ionophores, elevate [Ca 2ϩ ] i , cause formation of DAGs, and stimulate MAPKs.…”

mentioning

confidence: 99%

The Aminosteroid Phospholipase C Antagonist U-73122 (1-[6-[[17-β-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) Potently Inhibits Human 5-Lipoxygenase in Vivo and in Vitro

Feißt¹,

Albert²,

Steinhilber³

et al. 2005

Mol Pharmacol

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U-73122 (1-[6-[[17-␤-3-methoxyestra-1,3,5(10)-trien-17-yl]amino] hexyl]-1H-pyrrole-2,5-dione) is a widely used antagonist of phosphoinositide-specific phospholipase C (PLC) and is frequently used to define a role of PLC in receptor-mediated elevation of intracellular calcium concentration ([Ca 2ϩ ] i ). In human polymorphonuclear leukocytes (PMNLs), U-73122 inhibited increases in [Ca 2ϩ ] i induced by G protein-coupled receptor (GPCR) agonists (N-formyl-methionyl-leucyl-phenylalanine or platelet-activating factor; IC 50 of Ϸ2 to 4 M), but it failed to suppress responses induced by ionomycin or thapsigargin. 5-Lipoxygenase (5-LO) is a Ca

show abstract

Differential actions of diacyl- and alkylacylglycerols in priming phospholipase A2, 5-lipoxygenase and acetyltransferase activation in human neutrophils

Cited by 37 publications

References 47 publications

Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids.

Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids.

Phospholipase A₂: Its Usefulness in Laboratory Diagnostics

The Aminosteroid Phospholipase C Antagonist U-73122 (1-[6-[[17-β-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) Potently Inhibits Human 5-Lipoxygenase in Vivo and in Vitro

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Differential actions of diacyl- and alkylacylglycerols in priming phospholipase A2, 5-lipoxygenase and acetyltransferase activation in human neutrophils

Cited by 37 publications

References 47 publications

Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids.

Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids.

Phospholipase A2: Its Usefulness in Laboratory Diagnostics

The Aminosteroid Phospholipase C Antagonist U-73122 (1-[6-[[17-β-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) Potently Inhibits Human 5-Lipoxygenase in Vivo and in Vitro

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Phospholipase A₂: Its Usefulness in Laboratory Diagnostics