DECIDUAL CELL/PLACENTAL INTERACTIONS

蜕膜细胞/胎盘相互作用

• 批准号: 3469865
• 负责人: JOAN Sherar HUNT
• 金额: $ 11.21万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3469865
• 关键词: cell cell interaction; cell growth regulation; cell migration; centrifugation; cyclic AMP; cytotoxicity; decidua; embryo /fetus membrane; epidermal growth factor; flow cytometry; gene expression; gestational age; histology; in situ hybridization; laboratory rat; macrophage; microscopy; mixed tissue /cell culture; nucleic acid probes; placenta; pregnancy; pregnancy loss; protooncogene; radioimmunoassay; radiotracer; statistics /biometry; tissue /cell culture; transforming growth factors; trophoblast; uterus

Implantation signals a massive cellular response in the uterus. Among the major cell types that expand in response to pregnancy are macrophages, cells with both primitive and highly sophisticated functions. Macrophages that arrive via the blood or replicate in situ distribute themselves into specific anatomic compartments of pregnancy tissues, where they display distinct sets of phenotypic markers. The function(s) of uterine macrophages are unknown although their counterparts in other tissues protect against infection, a primitive function, and display or secrete molecules with powerful regulatory effects on other cells, a highly sophisticated function. This study is based on the postulate that uterine macrophages and invading trophoblast cells exert reciprocal influences over one another as the placental bed is established, maintained, and at term, dissolved. Preliminary data have been acquired which suggest that trophoblast cells are targets for some macrophage-derived molecules, and that trophoblast cells may influence some major macrophage activities. Preliminary data were generated in a rat model in which macrophages and their soluble products were cocultured with trophoblast cells in vitro. The proposed studies use the same general approach: uterine cells are harvested from pregnancy tissues (decidua, metrial gland, uterus) at mid to late gestation as well as from deciduoma and are fractionated into macrophage-enriched and macrophage-depleted populations; placental cells are represented by trophoblast cell lines derived from midgestation placentas of outbred and inbred rats and freshly harvested cells from mid to late gestation placentas. Both direct cellular effects and the effects of soluble molecules are tested using in vitro assays that focus on specific cellular activities, primarily proliferation and migration. Testing includes determining which molecules are normally synthesized by uterine macrophages (products of arachadonate metabolism, interleukin-1, tumor necrosis factor-alpha, colony stimulating factors). Identification of specific regulatory molecules is made by using highly purified and recombinant macrophage-derived molecules and monoclonal antibodies to those molecules. The mechanisms by which regulation is accomplished will be explored using cytotoxicity assays, determination of changes in ploidy and expression of specific markers, cAMP assays, and evaluation of proto-oncogene expression. Do negative macrophage-derived regulatory molecules prevent a dangerous influx of trophoblast cells into maternal tissues? Do positive regulatory molecules enhance successful pregnancy stimulating trophoblast cells? Future therapeutic interventions in cases of excessive trophoblast invasion (hydatidiform mole, choriocarcinoma) and in cases of chronic pregnancy failure may rely on the findings made in this study of uterine macrophages and similar studies addressing the roles of other types of uterine cells.

着床标志着子宫内大量细胞反应。 其中 因怀孕而扩张的主要细胞类型是巨噬细胞， 具有原始和高度复杂功能的细胞。巨噬细胞 通过血液到达或原位复制并将其自身分布到 妊娠组织的特定解剖结构，它们在其中展示 不同的表型标记集。子宫巨噬细胞的功能 尽管它们在其他组织中的对应物可以防止 感染，一种原始功能，并展示或分泌分子 对其他细胞具有强大的调节作用，这是一种高度复杂的 功能。这项研究基于以下假设：子宫巨噬细胞和 入侵的滋养层细胞相互影响，如 胎盘床被建立、维持，并在足月时溶解。 已获得的初步数据表明滋养层细胞 是一些巨噬细胞衍生分子的靶标，并且滋养层 细胞可能影响一些主要的巨噬细胞活动。初步数据是 在大鼠模型中产生，其中巨噬细胞及其可溶性产物 与滋养层细胞在体外共培养。拟议的研究使用 相同的通用方法：从妊娠期采集子宫细胞 妊娠中后期的组织（蜕膜、子宫腺、子宫） 来自蜕膜瘤并被分离成富含巨噬细胞的和 巨噬细胞耗尽的人群；胎盘细胞代表为 滋养层细胞系源自远交和妊娠中期胎盘 近交系大鼠和妊娠中期至晚期新鲜收获的细胞 胎盘。直接细胞效应和可溶性物质的效应 使用专注于特定细胞的体外测定来测试分子 活动，主要是扩散和迁移。测试包括 确定哪些分子通常由子宫巨噬细胞合成 （花生四烯酸代谢产物、白介素-1、肿瘤坏死 因子-α，集落刺激因子）。具体识别 调节分子是通过使用高度纯化和重组制成的 巨噬细胞衍生的分子和这些分子的单克隆抗体。 将通过以下方式探索实现监管的机制： 细胞毒性测定、倍性变化和表达的测定 特异性标记物、cAMP 测定和原癌基因表达评估。 巨噬细胞衍生的负调节分子是否可以预防危险的 滋养层细胞流入母体组织？做好积极监管 分子增强成功妊娠刺激滋养层细胞？ 滋养层过度侵袭病例的未来治疗干预 （葡萄胎、绒毛膜癌）和慢性妊娠的情况 失败可能依赖于这项子宫巨噬细胞研究的结果 以及解决其他类型子宫细胞作用的类似研究。