Cytoplasmic Lipid Bodies in Eosinophils: Central Roles in Eicosanoid Generation

Abstract

Background: Lipid bodies are lipid–rich cytoplasmic inclusions which form in diverse cell types, including eosinophils. Lipid body numbers increase in vivo in leukocytes participating in inflammatory processes. Our interest in lipid bodies relates to the roles that these structures play in arachidonate metabolism by eosinophils and other leukocytes involved in inflammation. Methods: Specific agonists, platelet–activating factor (PAF), two cis–unsaturated fatty acids (arachidonic and oleic acids) and a diglyceride (1–oleyl–2–acetyl–glycerol (OAG)), were used to stimulate lipid body formation in human eosinophils. Lipid bodies were enumerated and eosinophils were stimulated with submaximal calcium ionophore to generate leukotriene C₄ (LTC₄), which was quantitated by immunoassay. Results: Lipid body formation was rapidly inducible in eosinophils by specific intracellular signaling pathways. PAF, the two cis–unsaturated fatty acids and OAG each stimulated lipid body formation in eosinophils. Increased numbers of lipid bodies correlated quantitatively with the ‘priming’ response of eosinophils to form enhanced amounts of the 5–lipoxygenase–derived eicosanoid, LTC₄. Conclusion: Lipid bodies in eosinophils function as intracellular domains that are both depots of esterified arachidonate and sites at which regulated enymatic events relevant to arachidonate metabolism can occur. In conjunction with our findings that key eicosanoid–forming enzzymes, including cyclooxygenase, 5– and 15–lipoxygenase and LTC₄ synthase, are localized at lipid bodies in eosinophils, the finding that induction of lipid body formation correlated quantitatively with enhanced LTC₄ production indicate that lipid bodies are structurally distinct, inducible, non–nuclear sites for enhanced synthesis of paracrine eicosanoid mediators of inflammation.