LEUKOCYTE LIPID BODIES - STRUCTURE AND FUNCTION AS "EICOSASOMES"

Abstract

Lipid bodies are cytoplasmic inclusions that develop within leukocytes, including eosinophils and neutrophils, associated with inflammation. Our investigations of the formation and function of lipid bodies have revealed that they are distinct, inducible endoplasmic reticulum-derived, membrane- and ribosome-containing organelles with diverse functional roles in inflammatory responses of leukocytes. Leukocyte lipid bodies contain all enzymes required for synthesizing cyclo-oxygenase- and lipoxygenase-derived eicosanoids. Lipid body formation, rapidly inducible in vitro and in vivo by specific intracellular signaling pathways, enhances leukocyte formation of cyclo-oxygenase- and lipoxygenase-derived eicosanoids. Lipid bodies are discrete sites of eicosanoid synthesis, as documented for immunolocalized leukotriene C₄, leukotriene B_4, and prostaglandin E₂. Lipid body-derived eicosanoids function as both paracrine and intracrine mediators of inflammation. Based on combined proteomic and ultrastructural studies, leukocyte lipid bodies are complex organelles with internal membranes and ribosomes. Structurally and functionally leukocyte lipid bodes are distinct from lipid droplets in adipocytes.

Fig. 1

Pathways of lipid body formation in neutrophils (polymorphonuclear leukocytes) and eosinophils. Stimuli include platelet activating factor, cis fatty acids and diglycerides (OAG). Abbreviations: PAF, platelet activating factor; WEB, ; CV, ; PTX, pertussis toxin; 5-LO, 5-lipoxygenase; DEC, diethylcarbamazine; NDGA, ; MK866, ; ASA, aspirin; NSAIDs, non-steroidal anti-inflammatory drugs; COX, cyclo-oxygenase; OAG, oleoyl-acetyl glycerol; PLC, phospholipase C; PKC, protein kinase C; 5-HETE, 5-hydroxyeicosatetraenoic acid; D609, ; U7312, .