ROLE OF ENDOGENOUS LEUKOTRIENE PRODUCTION IN LYMPHOCYTE

这项提案的目的是确定 花生四烯的白三烯等脂氧合酶代谢产物 酸在人T细胞的活化和增殖中的作用。大多数 工作包括准确地定义什么是花生四烯酸 代谢物由T细胞产生。我和我的同事最近 发现外源花生四烯酸实质上和在 某些病例通过以下途径完全抑制白三烯B4(LTB4)的产生 有丝分裂刺激的T细胞。由于之前发表的所有研究 对T细胞花生四烯酸代谢的影响 外源花生四烯酸加入到培养基中，这就要求进入 普遍接受的概念中的问题，即T细胞不 主要代谢花生四烯酸。我们的预赛 结果表明，LTB4是花生四烯酸的主要代谢产物 T细胞的数量。在这项研究中，我将尝试描述所有 人T细胞和T细胞系的花生四烯酸代谢 使用高效液相色谱(HPLC)和 放射免疫分析(RIA)。T细胞会受到多种因素的刺激 包括有丝分裂原，抗原，钙离子载体， 白介素1(IL-1)和IL-2。单核细胞衍生因子的作用 在T细胞中，LTB4的产生也将被评估。 我还将继续我的初步研究，以确定 内源性LTB4在T细胞增殖中的作用初步结果 该提案中所描述的强烈表明内源性LTB4 生产是T细胞增殖的必要组成部分 对有丝分裂原的反应。LTB4是植物血凝素所必需的 (PHA)诱导IL-2的产生，但它也可能在 活化的T细胞对IL-2的反应。未来的研究将检查 白介素2和白介素4产生的精确关系 和T细胞对不同刺激的反应，包括 所谓的IL-2非依赖性有丝分裂原。两者都是人类外设 血液T细胞和各种人和小鼠T细胞株将 在这些实验中使用。

The purpose of this proposal is to determine the role of leukotrienes and other lipoxygenase metabolites of arachidonc acid in human T cell activation and proliferation. Most of the work involves defining precisely what arachidonic acid metabolites are produced by T cells. I and my coworkers recently discovered that exogenous arachidonic acid substantially and in some cases totally inhibits leukotriene B4 (LTB4) production by mitogenstimulated T cells. Since all previously published studies on arachidonic acid metabolism of T cells included the addition of exogenous arachidonic acid to the culture media, this calls into question in generally accepted concept that T cells do not metabolize arachidonic acid in a major way. Our preliminary results show that LTB4 is the major arachidonic acid metabolize of T cells. In this study, I will attempt to characterize all arachidonic acid metabolities of human T cells and T cell lines using high performance liquid chromatography (HPLC) and radioimmunoassays (RIAs). T cells will be stimulated by a variety of compounds including mitogens, antigens, calcium ionophores, interleukin 1 (IL-1) and IL-2. The role of moncyte derived factors in T cell production of LTB4 will also be assessed. I will also continue my preliminary studies on the precise role of endogenous LTB4 in T cell proliferation. Preliminary results described in the proposal strongly suggest that endogenous LTB4 production is a necessary component of T cell proliferation in response to mitogens. LTB4 is necessary for phytohemagglutinin (PHA) induced IL-2 production, but it may also have a role in the response of activated T cells to IL-2. Future studies will examine the precise relationship between LTB4 production, IL-2 production and T cell proliferation in response to different stimuli, including so-called IL-2 independent mitogens. Both human peripheral blood T cells and a variety of human and murine T cell lines will be used in these experiments.