Cytoplasmic Lipid Bodies of Inflammatory Cells

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DESCRIPTION (provided by applicant): Lipid bodies are ill-understood, lipid-rich cytoplasmic organelles characteristically more abundant in vivo in leukocytes and other cells associated with inflammatory reactions. Ongoing investigations of the formation and function of these enigmatic intracellular structures demonstrate that lipid bodies have distinct functional roles as specialized, inducible organelles active in inflammatory responses of leukocytes and other cells. Lipid bodies are sites of enhanced eicosanoid formation that function as both intracrine/autocrine and paracrine mediators of inflammatory responses. Therefore, of pertinence to cells involved in inflammation, lipid bodies are distinct intracellular organelles whose formation within cells is rapidly and specifically inducible making them "early response" structures, active as discrete intracellular loci involved in the regulated formation of eicosanoids. The investigations will use a combination of biochemical, ultrastructural, cytochemical, molecular biological and proteomic approaches to study lipid bodies in leukocytes and other cell types, both in situ within cells and as isolated subcellular structures. The goals will be to: 1) study the regulated formation and function of eicosanoids within lipid bodies, and 2) study the biogenesis and formation of lipid body organelles in leukocytes. The planned investigations will define the roles of lipid bodies as dynamic, inducible intracellular organelles active in the regulated metabolism of arachidonic acid and in other acute inflammatory responses of cells. Understanding the functions of lipid bodies will help elucidate mechanisms responsible for the heightened formation of biologically-active eicosanoid mediators, especially those involved in inflammatory reactions.