Cytoplasmic Lipid Bodies of Inflammatory Cells

描述（由申请人提供）：脂质小体是一种不为人所知的富含脂质的细胞器，其特征是在体内白细胞和其他与炎症反应相关的细胞中更为丰富。对这些神秘的细胞内结构的形成和功能的持续研究表明，脂质体在白细胞和其他细胞的炎症反应中作为特化的、可诱导的细胞器具有独特的功能作用。脂质体是类二十烷类蛋白形成增强的部位，在炎症反应中扮演分泌内/自分泌和分泌旁介质的角色。因此，与参与炎症的细胞相关，脂质体是独特的细胞内细胞器，其在细胞内的形成是快速和特异性诱导的，使其成为“早期反应”结构，作为离散的细胞内位点活跃，参与调节类二十烷的形成。这些研究将结合生物化学、超微结构、细胞化学、分子生物学和蛋白质组学的方法来研究白细胞和其他细胞类型中的脂质体，包括细胞内的原位和分离的亚细胞结构。我们的目标是：1)研究脂质体中类二十烷的形成和功能的调控；2)研究白细胞中脂质体细胞器的生物发生和形成。计划中的研究将定义脂质体的作用为动态的、可诱导的细胞内细胞器，活跃于花生四烯酸的调节代谢和细胞的其他急性炎症反应中。了解脂质体的功能将有助于阐明生物活性类二十烷酸介质的形成机制，特别是那些参与炎症反应的机制。

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.