FUNCTIONS OF PREGNANCY SPECIFIC GLYCOPROTEINS

妊娠特异性糖蛋白（PSG）是一个分泌性糖蛋白家族， 胎盘产生的蛋白质。 这些蛋白质属于 免疫球蛋白基因超家族，是成功的免疫球蛋白基因的关键。 怀孕 在许多物种中观察到PSG的表达 包括人类和老鼠。 我们的长期目标是定义 妊娠特异性糖蛋白在正常妊娠中的作用及其机制 和异常妊娠。 本申请的目的是 表征PSG与受体承载的初始相互作用 靶细胞克隆其受体，克隆其受体， 评估它们调节细胞因子和其他细胞因子的产生的能力， 炎症介质。 应用程序的中心假设 PSG与靶细胞上的特定细胞受体结合， 这种相互作用有助于调节免疫和 正常妊娠所必需的炎症介质 结果。 拟议研究背后的基本原理是，PSG是 通过与单核细胞上的特定细胞受体结合而参与其中 吞噬细胞在调节免疫应答的介质中的作用，例如 IL-10，从而防止胎儿胎盘损伤， 局部发炎 治疗药物的未来发展 干预措施，旨在操纵免疫调节作用， 怀孕期间的PSG，将取决于具体PSG的仔细定义 功能协调发展的 为了实现本申请的目标，我们将 本研究的目的有两个：（1）克隆和鉴定编码 鼠巨噬细胞上鼠PSG的细胞受体;（2） 表征鼠PSG 2、PSG 3和PSG 4以及人PSG 6的作用， 体外免疫调节剂。我们希望所取得的成果将有助于 在定义这种糖蛋白家族在 保持正常怀孕，这一知识将导致 开发与管理相关的新治疗策略， 复杂的怀孕

Pregnancy specific glycoproteins (PSGs) are a family of secreted proteins produced by the placenta. These proteins belong to the immunoglobulin gene super family and are essential for a successful pregnancy. Expression of PSGs has been observed in many species including humans and mice. Our long-range goal is to define the roles and mechanisms of action of pregnancy specific glycoproteins in normal and abnormal pregnancy. The objective of this application is to characterize the initial interaction of PSGs with receptor-bearing target cells to clone their receptor, to clone their receptor, and to evaluate their ability to regulate the production of cytokines and other mediators of inflammation. The central hypothesis of the application is that PSGs bind to a specific cellular receptor on target cells and that this interaction contributes to the regulation of immune and inflammatory mediators which are essential for a normal pregnancy outcome. The rationale behind the proposed research is that PSGs are involved, through binding to a specific cellular receptor on mononuclear phagocytes in modulating mediators of the immune response, such as IL-10, thereby preventing the feto-placental damage that could ensue from local inflammation. The future development of therapeutic interventions, aimed at manipulation of immunomodu-latory effects of PSGs during pregnancy, will depend on careful definition of specific PSG functions. To accomplish the objectives of this application, we will pursue two specific aims: (1) Clone and characterize the cDNA encoding the cellular receptor for murine PSGs on murine macrophages; (2) Characterize the roles of murine PSG2, PSG3, and PSG4 and human PSG6 as immunomodulators in vitro. We expect that the results obtained will aid in the definition of the roles of this glycoprotein family in maintaining normal pregnancy and that this knowledge will result in the development of new therapeutic strategies related to the management of complicated pregnancies.