DECIDUAL CELL/PLACENTAL INTERACTIONS

植入标志着子宫内的大规模细胞反应。在这些人中 因怀孕而扩张的主要细胞类型是巨噬细胞， 既具有原始功能又具有高度复杂功能的细胞。巨噬细胞 通过血液到达或在原位复制将自己分配到 妊娠组织的特定解剖隔间，在那里它们显示 不同的表型标记集合。子宫巨噬细胞的功能(S) 是未知的，尽管它们在其他组织中的对应物可以保护 感染，一种原始功能，并显示或分泌分子与 强大的对其他细胞的调节作用，高度复杂 功能。这项研究基于这样的假设：子宫巨噬细胞和 侵入的滋养层细胞相互影响，如 胎盘床建立、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，而滋养层细胞 细胞可能会影响一些主要的巨噬细胞活动。初步数据为 在大鼠模型中产生巨噬细胞及其可溶性产物 与滋养层细胞体外共培养。拟议的研究使用 同样的一般方法：子宫细胞是从怀孕中获取的 妊娠中后期的组织(蜕膜、子宫腺、子宫) 如蜕膜瘤，并被分成富含巨噬细胞和 巨噬细胞耗竭的群体；胎盘细胞由 异种和异种母猪胎盘来源的滋养层细胞系 近交系大鼠和妊娠中晚期新鲜采集的细胞 胎盘。直接的细胞效应和可溶性的影响 分子的测试使用的是体外测试，主要集中在特定的细胞上。 活动，主要是扩散和移徙。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)。识别特定的 调节分子是通过使用高度纯化和重组的 巨噬细胞衍生的分子和针对这些分子的克隆抗体。 完成监管的机制将使用以下工具进行探索 细胞毒性试验，倍体变化和表达的测定 特异性标记物、cAMP分析和原癌基因表达的评估。 负性巨噬细胞衍生的调节分子能防止危险的 滋养层细胞流入母体组织？实施积极的监管 分子增强成功的妊娠刺激滋养层细胞？ 滋养细胞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 失败可能取决于这项对子宫巨噬细胞的研究结果 以及解决其他类型子宫细胞的作用的类似研究。

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.