PERITONEAL MACROPHAGE MIGRATION IN ENDOMETRIOSIS

这项研究的长期目标是促进我们对 子宫内膜异位症的发生和相关的不孕症。 的 研究将集中在与此相关的不孕症的原因上。 疾病 许多过去的研究表明， 子宫内膜异位症的女性含有大约十倍的 巨噬细胞，如在无疾病的可生育患者中所见。 进一步 研究强烈表明，这些活化的巨噬细胞可以 表现出几种对成功有害的活动 生殖 本研究的中心重点将是识别 负责定向迁移或趋化的机制 巨噬细胞进入腹膜 初步数据显示， 巨噬细胞的浓度和活性显著增加 趋化因子在腹膜液的患者患有 子宫内膜异位症，当与正常生育对照或患者相比， 医学治疗 进一步的研究表明，这种趋化性 活性通常在黄体期的基质细胞中表达， 在增殖期不存在。 然而，在患有 子宫内膜异位症增生期子宫内膜表现为高 趋化活性 本研究的总体具体目标是 阐明该因子调节 子宫内膜异位症妇女腹腔巨噬细胞的数量和活性。 具体目标是通过以下方式分离和表征该因素： 蛋白纯化、N-末端氨基酸序列分析和cDNA 克隆。 负责产生这种因子的细胞将 通过免疫组织化学分析和蛋白质合成确定。 的 在增生组织和正常组织中调节该因子 将通过蛋白质合成和RNA分析来检查子宫内膜。 除了负责表达这一点的机制外， 还将进行因素研究，以确定 该因子与巨噬细胞相互作用。 这些研究将审查 这种因子激活巨噬细胞并指导它们的 迁移 还将检查趋化因子/巨噬细胞相互作用 在细胞表面受体的水平上。 研究将针对 通过分离和表达克隆来表征受体。 我们的假设是，在巨噬细胞中存在一种趋化因子， 在子宫内膜异位症患者中表达不当。 此外，这种趋化因子可以通过以下途径激活巨噬细胞： 与特定的细胞表面受体结合。 这些结果将定义 巨噬细胞向腹膜浸润的机制。 对趋化因子的性质有了深入的了解， 其表达的调节，以及与其相互作用的机制 巨噬细胞将为治疗方法的发展开辟新的可能性， 用于治疗子宫内膜异位症和相关的不孕症。

The long term objective of this research is to advance our understanding of the occurrence of endometriosis and the associated infertility. The research will focus on the cause of the infertility associated with this disease. Many past studies have indicated that the peritoneal fluid of women with endometriosis contains approximately ten times the number of macrophages as is seen in the disease free fertile patient. Further studies have strongly indicated that these activated macrophages can display several activities which are deleterious to successful reproduction. The central focus of this study will be the identification of the mechanism responsible for the directed migration or chemotaxis of macrophages to the peritoneum. Preliminary data have demonstrated a significant increase in the concentration and activity of a macrophage chemotactic factor in the peritoneal fluid of patients suffering from endometriosis, when compared with normal fertile controls or patients on medical treatments. Further studies have indicated that this chemotactic activity is normally expressed in the stromal cells of the luteal phase and is absent in the proliferative phase. However, in patients with endometriosis the proliferative phase endometrium demonstrates high chemotactic activity. The overall specific aim of this study is to elucidate the possible mechanism(s) by which this factor modulates the number and activity of peritoneal macrophages in women with endometriosis. The specific aims are to isolate and characterize this factor through protein purification, N-terminal amino acid sequence analysis and CDNA cloning. The cells responsible for the production of this factor will be determined through immunohistochemical analysis and protein synthesis. The regulation of this factor in the endometriotic tissue and in the normal endometrium will be examined through protein synthesis and RNA analysis. In addition to the mechanism(s) responsible for the expression of this factor studies will also be performed to determine the mechanism by which this factor interacts with macrophages. These studies will examine the ability of this factor to activate macrophages as well as direct their migration. Chemotactic factor/macrophage interaction will also be examined at the level of cell surface receptors. Studies will be directed at the characterization of the receptor through isolation and expressing cloning. Our hypothesis suggests that there exists a macrophage chemotactic factor which is inappropriately expressed in women with endometriosis. Furthermore, this chemotactic factor can activate macrophages through binding to a specific cell surface receptor. These results will define the mechanism involved in the infiltration of macrophages into the peritoneum. A solid understanding of the nature of the chemotactic factor, the regulation of its expression, and the mechanism by which it interacts with macrophages will open new possibilities for the development of therapies for the treatment of endometriosis and the associated infertility.