MACROPHAGES, OXIDATION, AND ENDOMETRIOSIS

子宫内膜异位症是一种常见的疾病，造成疼痛和痛苦， 通常是女性不孕的原因。有一个共识， 逆行性月经可能解释子宫内膜细胞的存在 在腹膜腔内。然而，关于病因学知之甚少 疾病或为什么这种疾病只发生在某些妇女，尽管 在大多数女性中常见的逆行月经。这个程序 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 扩展为创新的具体目标， 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， 巨噬细胞清除剂功能的妇女腹腔 子宫内膜异位症是负责生存和生长的异位 子宫内膜项目2提出了一种积极的机制， 腹膜液的成分可能加剧氧化环境， 有利于单核细胞的募集和细胞的生长， 子宫内膜细胞该项目表明，存在轻度氧化 腹膜液中的脂蛋白成分。项目3提出， CSF-1可能同时发挥自分泌和旁分泌的作用，不仅促进 子宫内膜细胞的生长，而且在保护巨噬细胞 从而增加它们在腹膜中的存活 腔项目4将研究巨噬细胞的药理学调节 清道夫功能、细胞因子的产生和子宫内膜细胞生长。 抗氧化剂、激素和类维生素A对这些功能的影响 将被确定。项目5，微型临床项目将建立 氧化应激标志物在小鼠中的存在和差异 子宫内膜异位症受试者和对照的血浆。该项目还将 评估抗氧化剂改变这些水平的功效 标记。该计划由一个行政核心和一个 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.