MACROPHAGES, OXIDATION, AND ENDOMETRIOSIS

子宫内膜异位症是一种常见的疾病，会引起疼痛和痛苦， 通常是女性不孕不育的原因。有一种共识是 月经逆行可能是子宫内膜细胞存在的原因 在腹膜腔内。然而，人们对其病因知之甚少。 或者为什么这种疾病只发生在某些女性身上，尽管 月经逆行在大多数女性中常见。本节目 有五个项目，提出了关于事件的新假设 可能导致子宫内膜异位症病变的建立。这些想法是 扩展为创新的特定目标，将使用 生物化学、免疫学和分子生物学技术。 项目1提出子宫内膜细胞的根本性改变和 巨噬细胞清除剂对女性腹腔炎的清除作用 子宫内膜异位症是异位生存和生长的主要原因 子宫内膜。项目2提出了一种积极的机制，通过这种机制， 腹腔液的成分可能会加剧氧化环境， 有利于单个核细胞的募集和细胞的生长 子宫内膜细胞。这一项目表明存在轻度氧化的 腹腔液中的脂蛋白成分。项目3建议 CSF-1可能同时发挥自分泌和旁分泌作用，不仅促进 子宫内膜细胞的生长也在保护巨噬细胞 从细胞凋亡性死亡，从而增加它们在腹膜中的存活率 空洞。项目4将研究巨噬细胞的药理调节。 清道夫功能、细胞因子的产生和子宫内膜细胞的生长。 抗氧化剂、激素和维甲酸对这些功能的影响 将会被确定。项目5，迷你临床项目将建立 氧化应激标志物在老年人中的存在及差异 子宫内膜异位症患者和对照组的血浆。该项目还将 评估抗氧化剂改变这些物质水平的效果 记号笔。该计划由一个管理核心和一个 组织/细胞培养核心。

Endometriosis is a common disorder that inflicts pain and suffering and is often the cause of infertility in women. There is a consensus that retrograde menstruation may account for the presence of endometrial cells in the peritoneal cavity. However, little is known regarding the etiology of the disease or why the disease occurs only in certain women despite the common occurrence of retrograde menstruation in most women. This program has five projects that propose novel hypotheses regarding the events that may lead to the establishment of endometriosis lesions. These ideas are extended as innovative specific aims that would be addressed using biochemical, immunological, and molecular biological techniques. Project 1 proposes that fundamental alterations in endometrial cell and macrophage scavenger functions to the peritoneal cavity of women with endometriosis are responsible for the survival and growth of the ectopic endometrium. Project 2 proposes an active mechanism by which intrinsic components of the peritoneal fluid may exacerbate an oxidative milieu that is conducive to the recruitment of mononuclear cells and the growth of the endometrial cells. This project suggests the presence of mildly oxidized lipoprotein components in the peritoneal fluid. Project 3 proposes that CSF-1 may play both autocrine and paracrine roles in promoting not only the growth of the endometrial cells but also in protecting macrophages from apoptotic death thereby increasing their survival in the peritoneal cavity. Project 4 will study the pharmacological regulation of macrophage scavenger function, production of cytokines, and endometrial cell growth. The effects of antioxidants, hormones, and retinoids on these functions will be determined. Project 5, the mini clinical project will establish the presence and differences in the markers of oxidative stress in the plasma of endometriosis subjects and controls. This project will also evaluate the efficacy of antioxidants to alter the levels of these markers. The program is supported by an administrative core and a tissue/cell culture core.