EARLY HEMATOPOIETIC CELL REGULATORS OF HUMAN ORIGIN

本项目的目的是研究早期造血的作用， 细胞调节因子如红细胞爆发促进活性 (BPA巨核细胞集落刺激因子（MEF-CSF）和集落 脾形成单位（CFU-S）存活增强因子（CFU-S-F）与 造血细胞的复制、定型和分化 祖细胞 它旨在实现以下目标： 逐步纯化和表征源自人的相关因子 尿液和人单核细胞条件培养基 包括尺寸选择性超滤，分级沉淀， 层析和超离心。 研究的作用机制 这些因素，例如可逆性、时程、剂量 依赖性的程序，涉及预孵育的靶细胞， 用促红细胞生成素（EPO）激发因子进行悬浮培养 在半固体培养基培养物中的细胞或测定细胞的 CFU-S含量。 确定红细胞数量的增加是否 由这些因素引起的爆发形成单位（BFU-E）或CFU-S， 基于细胞复制或基于细胞活化（致敏）。 研究因子的靶细胞性质（直接与 间接作用，单能对多能祖细胞）。 研究 在不同的阶段， 洁净. 研究拟订《公约》的机制， 因素，并确定其生理和临床意义。 到 将该终末细胞群分级分离， 适当的体外刺激。 BPA、MEG-CSF和CFU-S-F含量 贫血、红细胞增多症和血小板异常患者的尿液 对不同原因和正常个体进行测量， 可能与其他血液学参数相关。 血液 病人的单核细胞将被测试产生BPA的能力 PHA治疗后，以及对BPA的反应能力， 直接和预孵育BFU-E试验，以确定是否 这些测量提供了临床上有用的信息。 基于 在本项目分析过程中获得的信息， 将得到进一步发展。

The objective of this project is to study the roles early hematopoietic cell regulatory factors such as erythroid burst promoting activities (BPA's) megakaryocyte colony stimulating factor (MEF-CSF) and colony forming unit spleen (CFU-S) survival enhancing factor (CFU-S-F) play with respect to the replication, commitment and differentiation of hematopoietic progenitor cells. It is intended to pursue the following aims: Isolate, progressively purify and characterize relevant factors derived from human urine and from human mononuclear cell conditioned media by techniques involving size selective ultrafiltration, fractional precipitation, chromatography and ultracentrifugation. Study the mechanism of action of these factors, e.g. with respect to reversibility, time course, dose dependence by procedures involving preincubation of the target cells in suspension culture with a factor followed by erythropoietin (EPO) challenge of the cells in semi-solid medium culture or assay of the cells for their content of CFU-S. Determine whether the increase in numbers of erythroid burst forming units (BFU-E) or CFU-S brought about by these factors is based on cell replication or on cell activation (sensitization). Investigate the nature of the target cells for the factors (direct vs. indirect action, unipotent vs. multipotent progenitor cells). Study the specificity of the factors of the factors, at various stages of purification. Study the mechanisms governing the elaboration of the factors and ascertain their physiological and clinical significance. To this end cell populations will be fractionated and the isolates subjected to appropriate stimuli in vitro. The BPA, MEG-CSF and CFU-S-F content of urine from patients with anemias, polycythemias and platelet disorders due to different causes and from normal individuals will be measured to detect possible correlations with other hematological parameters. The blood mononuclear cells of patients will be tested for the ability to produce BPA after PHA treatment and also for the ability to respond to BPA in the direct and the preincubation BFU-E assays in order to find out whether these measurements provide clinically useful information. Based on information gained in the course of this project assays for the factors will be further developed.