Role of Arachidonyl Triglycerides within Lipid Bodies in Eicosanoid Formation by Human Polymorphonuclear Cells

Johnson, Margaret M.; Vaughn, Ben; Triggiani, Massimo; Swan, Dennis D.; Fonteh, Alfred N.; Chilton, Floyd H.

doi:10.1165/ajrcmb.21.2.3489

Cited by 30 publications

(25 citation statements)

References 21 publications

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“…Interestingly, EETs influence neutrophil adherence in the low micromolar range (Pratt et al 2002). Since both arachidonate and linoleate are present in relatively high abundance in their esterified forms in neutrophil phospholipids (Yano et al 1983;Johnson et al 1999), it does not seem unreasonable to propose that either esterified DiHOMEs and/or esterified DHETs represent inhibitory signals with respect to the neutrophil NADPH oxidase activation, nor to speculate that other similar membrane-associated systems such as the plant NADPH oxidase or the mitochondrial respiratory chain are regulated in a similar fashion. 9(10)-/12(13)-EpOME stimulates the neutrophil respiratory burst.…”

Section: Discussionmentioning

confidence: 99%

Dihydroxyoctadecamonoenoate esters inhibit the neutrophil respiratory burst

Hammock

2007

J Biosci

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The leukotoxins [9(10)-and 12(13)-EpOME] are produced by activated inflammatory leukocytes such as neutrophils. High EpOME levels are observed in disorders such as acute respiratory distress syndrome and in patients with extensive burns. Although the physiological significance of the EpOMEs remains poorly understood, in some systems, the EpOMEs act as a protoxin, with their corresponding epoxide hydrolase metabolites, 9,10-and 12,13-DiHOME, specifically exerting toxicity. Both the EpOMEs and the DiHOMEs were also recently shown to have neutrophil chemotactic activity. We evaluated whether the neutrophil respiratory burst, a surge of oxidant production thought to play an important role in limiting certain bacterial and fungal infections, is modulated by members of the EpOME metabolic pathway. We present evidence that the DiHOMEs suppress the neutrophil respiratory burst by a mechanism distinct from that of respiratory burst inhibitors such as cyclosporin H or lipoxin A4, which inhibit multiple aspects of neutrophil activation.

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Section: Discussionmentioning

confidence: 99%

Dihydroxyoctadecamonoenoate esters inhibit the neutrophil respiratory burst

Hammock

2007

J Biosci

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“…Together, our findings support a role for lipid bodies to function as specific sites for eicosanoid formation. Of special interest for inflammatory cells where increased eicosanoid synthesis is observed, lipid body arachidonyl phospholipids might provide a source of substrate AA without requiring the perturbation of the integrity of membranes and could be replenished from the arachidonyl triglycerides abundant in lipid bodies (59,60).…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-Induced Leukocyte Lipid Body Formation In Vivo: Innate Immunity Elicited Intracellular Loci Involved in Eicosanoid Metabolism

Pacheco

Bozza

Gomes

et al. 2002

The Journal of Immunology

134

172

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Lipid bodies are rapidly inducible, specialized cytoplasmic domains for eicosanoid-forming enzyme localization, which we hypothesize to have specific roles in enhanced inflammatory mediator production during pathological conditions, including sepsis. However, little is known about the origins, composition, or functions of lipid bodies in vivo. We show that lipid body numbers were increased in leukocytes from septic patients in comparison with healthy subjects. Analogously, the intrathoracic administration of LPS into mice induced a dose- and time-dependent increase in lipid body numbers. Pretreatment with anti-CD14 or anti-CD11b/CD18 mAb drastically inhibited LPS-induced lipid body formation. Moreover, LPS failed to form lipid bodies in C3H/HeJ (TLR4 mutated) mice, demonstrating a requisite role for LPS receptors in lipid body formation. LPS-induced lipid body formation was also inhibited by the platelet-activating factor-receptor antagonists, suggesting a role for endogenous platelet-activating factor. The eicosanoid-forming enzymes, 5-lipoxygenase and cyclooxygenase-2, were immunolocalized within experimentally induced (LPS in mice) or naturally occurring (septic patients) lipid bodies. The proinflammatory cytokine involved in the pathogenesis of sepsis, TNF-α, was also shown to colocalize within lipid bodies. Prior stimulation of leukocytes to form lipid bodies enhanced the capacity of leukocytes to produce leukotriene B4 and PGE2. In conclusion, our studies indicate that lipid bodies formed after LPS stimulation and sepsis are sites for eicosanoid-forming enzymes and cytokine localization and may develop and function as structurally distinct, intracellular sites for paracrine eicosanoid synthesis during inflammatory conditions.

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“…Exposure of cells to low AA concentrations results in AA incorporation into primarily 1-acyl-linked phospholipid molecular species through a high affinity, low capacity enzymatic pathway. In contrast, exposure of cells to high levels of AA will result in the incorporation of AA into neutral lipid fractions (mainly TG) and the formation of 1,2-diarachidonoyl-sn-glycero-3-phosphocholine by a low affinity, high capacity pathway (42,71). Our data show that there is an increase in AA mass in the neutral lipid fractions of mast cells undergoing apoptosis.…”

Section: Discussionmentioning

confidence: 62%

“…AA Accumulation in Neutral Lipid Classes-Our previous studies suggested that inflammatory cells exposed to high concentrations of AA shuttled excess AA into neutral lipids, with triglycerides being the predominant class (42,43). To determine whether a similar pathway existed in BMMC, the neutral lipid fractions (Fig.…”

Section: Table Imentioning

confidence: 99%