FUNCTIONS OF PREGNANCY SPECIFIC GLYCOPROTEINS

妊娠特异性糖蛋白(PSG)是一类分泌型糖蛋白。 胎盘产生的蛋白质。这些蛋白质属于 免疫球蛋白基因和超家族是成功的必不可少的 怀孕了。PSGs在许多物种中都有表达 包括人类和老鼠。我们的长期目标是定义角色 妊娠特异性糖蛋白在正常人群中的作用机制 还有不正常的怀孕。此应用程序的目标是 PSG与受体载体的初始相互作用特征 靶细胞克隆它们的受体，克隆它们的受体，并 评估他们调节细胞因子和其他物质产生的能力 炎症的中介物。应用程序的中心假设 PSG与靶细胞上的特定细胞受体结合并 这种相互作用有助于调节免疫和 正常妊娠所必需的炎性介质 结果。这项拟议研究背后的理由是，PSG是 参与，通过与单个核细胞上的特定细胞受体结合 吞噬细胞在调节免疫反应的媒介中的作用，如 IL-10，从而防止随之而来的胎盘损伤 由局部炎症引起。治疗学的未来发展 干预措施，旨在操纵免疫调节效应 怀孕期间的PSG，将取决于对特定PSG的仔细定义 功能。为了实现本应用程序的目标，我们将 追求两个具体目标：(1)克隆和鉴定编码基因 小鼠巨噬细胞上多糖的细胞受体；(2) 鉴定小鼠PSG2、PSG3、PSG4和人PSG6作为 体外免疫调节剂。我们希望所取得的结果将有助于 在定义这个糖蛋白家族在 维持正常妊娠，这一知识将导致 开发与管理相关的新的治疗策略 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.