Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism.
Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositories of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.
Harvard Thorndike Laboratory, Department of Medicine, Beth Israel Deaconness Medical Center, Boston, MA, USA. pbozza@gen.dbbm.fiocruz.br
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Bozza
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Yu
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Weller
D016718:Arachidonic Acid / Q000378:metabolism* / Q000627:therapeutic use; D015777:Eicosanoids / Q000096:biosynthesis*; D004804:Eosinophils / Q000502:physiology*; D006801:Humans; D017681:Hypereosinophilic Syndrome; D007249:Inflammation; D018836:Inflammation Mediators / Q000502:physiology; D008563:Membrane Lipids / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*
D015777:Eicosanoids; D018836:Inflammation Mediators; D008563:Membrane Lipids; D016718:Arachidonic Acid