Pathways of Maternal Anemia

项目摘要 在热带国家，妊娠疟疾是一个压倒性的公共卫生问题，它与 母亲和她的孩子的疾病和死亡率。疟疾在原发人群中诱导炎症反应 妇女(患有这种疾病的人)。胎盘中高水平的肿瘤坏死因子与母体贫血有关 在初产妇中，但在多胎中不是。我们假设促炎信号通路在 初孕妇女改变胎盘中红细胞生成特异性因子的表达，导致贫血 通过以下一条或两条途径。1.炎性细胞因子和其他巨噬细胞介质 抑制调节红细胞生成的胎盘因子的表达。2.寄生虫与胎盘的粘连 合体滋养层细胞直接调节调节红细胞生成的胎盘因子的表达。 蛋白质组学研究构成了一种无偏见的方法来研究全球蛋白质表达的差异。 在这里，我们将检测与疟疾贫血途径相关的胎盘血浆蛋白质组的变化。 寄生虫隔离和炎症--胎盘。具体地说，这项研究将审查1. 应用定量蛋白质组学工具研究与疟疾贫血相关的胎盘血浆蛋白质组。2. 用定量蛋白质组学方法研究胎盘免疫细胞的分泌体。3.确认疟疾 在坦桑尼亚妇女队列中，贫血途径蛋白与疟疾贫血有关。基于这些 我们预期的假设是，转录因子、生长因子和 胎盘血中与红细胞生成相关的免疫调节剂将与母体血红蛋白相关 级别。我们预计，改变红系增殖和发育的巨噬细胞特异性介质将 在初孕妇女的胎盘血样中更为丰富。 妊娠期疟疾是人们最了解的疟疾综合征。人血浆蛋白质组特征的研究 感染疟疾的孕妇将有助于我们了解疟疾患者体内宿主与病原体的相互作用 怀孕宿主，并将为参与发病机制的新分子的更大研究提供信息 儿童严重贫血的风险。

Project Summary Pregnancy malaria is an overwhelming public health problem in tropical countries, which has been related to disease and mortality for both the mother and her child. Malaria induces inflammatory responses in primigravid women (who suffer from the disease). High TNF-¿ levels in the placenta are associated with maternal anemia in primigravidas but not in multigravidas. We hypothesize that proinflammatory signaling pathways in primigravid women modify the expression of erythropoiesis-specific factors in the placenta, leading to anemia through one or both of the following pathways. 1. Inflammatory cytokines and other macrophage mediators suppress the expression of placental factors that regulate erythropoiesis. 2. Parasite adhesion to placental syncytiotrophoblast directly modulates the expression of placental factors that regulate erythropoiesis. Proteomics studies constitute a nonbiased approach to investigate differences in global protein expression. Here we will examine placental plasma proteome changes related to malarial anemia pathway at the site of parasite sequestration and inflammation-the placenta. Specifically, the study will examine 1. Changes in placental plasma proteome associated with malarial anemia by using quantitative proteomics tools. 2. Characterize the secretome of placental immune cells by quantitative proteomics. 3. Confirm that malaria anemia pathway proteins are associated with malaria anemia in cohorts of Tanzanian women. Based on these hypotheses we expect, that the relative abundance of transcription factors, growth factors and immunomodulators in placental blood associated with erythropoiesis will correlate with maternal hemoglobin levels. We expect that macrophage-specific mediators that modify erythroid proliferation and development will be more abundant in placental blood samples from primigravidas. Pregnancy malaria is the best-understood malaria syndrome. The characterization of the plasma proteome in malaria-infected pregnant women will contribute to our understanding of the host-pathogen interaction in the pregnant host, and will generate information for larger studies of novel molecules involved in the pathogenesis of severe anemia in children.