CYTOPLASMIC LIPID BODIES OF INFLAMMATORY CELLS

人体细胞对花生四烯酸的代谢产生了许多 二十烷类衍生物可能不仅对内源的 不仅是细胞的功能，也是炎症和免疫的媒介。 这项拟议的研究将调查脂体在血管生成中的作用 中性粒细胞和嗜酸性粒细胞对花生四烯酸的代谢 白细胞。脂体无膜结合，大致呈球形。 可通过光和透射率识别的细胞质内含物 电子显微镜下的各种细胞类型。尽管人们认为 由脂质组成，这些细胞内的性质和功能 结构一直不为人知。最近的发现表明，这些脂质 小体，当细胞参与到体内时，它们的数量会增加 炎症反应，在摄取和并入 花生四烯酸。为了确定脂质小体在体内的作用 花生四烯酸的代谢，亚细胞分离的方法将 被开发用于将脂体与人中性粒细胞分离并 嗜酸性粒细胞。纯化后的脂体的脂类和蛋白质含量 这两种类型的白细胞将被确定。此外，使用 纯化、分离的脂体，参与酶的存在 花生四烯酸的酯化反应，花生四烯酸的释放 磷脂和二十烷类衍生物的生成，特别是 白三烯C4(用于嗜酸性粒细胞)和B4(用于中性粒细胞)，来自 花生四烯酸将被评估。利用纯化的人嗜酸性粒细胞 和中性粒细胞，这些细胞中脂体的形成将是 体外诱导，以及放射性标记的时间掺入 将评估进入脂体的磷脂前体和脂肪酸 通过电子显微镜放射自显影和中性成分分析 分离的脂体中的脂类和磷脂。.的存在 这些诱导的脂体中的白三烯和其他二十烷类化合物将被 评估过了。这些研究将确定细胞质脂质的组成 体内的这两个白细胞，并将评估之前的 未被认识的脂体在花生四烯酸代谢中的作用 这些细胞。因为在许多不同的细胞中发现了脂体，所以这些 研究，除了评估这些细胞质的功能 二十烷类介体在粒细胞生成中的包裹体与 炎症和免疫，可能会阐明这些更普遍的作用 在细胞花生四烯酸代谢中经常被忽视的细胞器。

The metabolism of arachidonic acid by human cells generates a number of eicosanoid derivatives that may be of importance not only to the endogenous functioning of cells but also as mediators of inflammation and immunity. The proposed research will investigate the role of lipid bodies in the metabolism of arachidonic acid by human neutrophilic and eosinophilic leukocytes. Lipid bodies are non-membrane bound, roughly spherical cytoplasmic inclusions that may be identified by light and transmission electron microscopy in a variety of cell types. Although believed to be composed of lipid, the nature and function of these intracellular structures have been unknown. Recent findings indicate that these lipid bodies, which increase in number in vivo when cells are involved in inflammatory reactions, are active in the uptake and incorporation of arachidonic acid. In order to define the role of lipid bodies in the metabolism of arachidonic acid, methods of subcellular fractionation will be developed to isolate lipid bodies from human neutrophils and eosinophils. The lipid and protein content of lipid bodies purified from these two types of leukocytes will be determined. In addition, using purified, isolated lipid bodies, the presence of enzymes involved in the esterification of arachidonic acid, the release of arachidonic acid from phospholipids and in the generation of eicosanoid derivatives, especially leukotrienes C4 (for eosinophils) and B4 (for neutrophils), from arachidonic acid will be evaluated. Utilizing purified human eosinophils and neutrophils, the formation of lipid bodies in these cells will be induced in vitro, and the temporal incorporation of radiolabeled phospholipid precursors and fatty acids into lipid bodies will be evaluated both by electron microscopic autoradiography and by analyses of neutral lipids and phospholipids in isolated lipid bodies. The presence of leukotrienes and other eicosanoids in these induced lipid bodies will be assessed. These studies will define the composition of cytoplasmic lipid bodies in these two leukocytes and will evaluate the previously unappreciated role of lipid bodies in the metabolism of arachidonic acid by these cells. Because lipid bodies are found in many different cells, these studies, in addition to assessing the function of these cytoplasmic inclusions in granulocyte generation of eicosanoid mediators pertinent to inflammation and immunity, may elucidate a more general role for these often overlooked organelles in cellular arachidonic acid metabolism.