REGULATION OF MYELOID PROGENITOR CELL DIFFERENTIATION

此应用程序将调查以下之间的关系 重组生长因子和抑制物在控制髓系细胞中的作用 对祖细胞增殖相互作用的认识 这些生物分子的作用对最终的临床很重要。 使用这些因子进行生物治疗。监管机构的干预作用 重组鼠和人生长因子G-CSF、GM-CSF、M-CSF (CSF1)白介素3和白介素1，以及抑制物和干扰素 α、β、γ肿瘤坏死因子与前列腺素 E(PCE)，在控制小鼠和人类造血中的作用 将研究祖细胞的增殖情况。一种新型的前列腺素E_2 诱导的造血抑制机制已被证实 完整的动物，对被压制具有广泛的影响 再生障碍性贫血、慢性贫血患者的造血功能 疾病和白血病。生长因子的类似能力 建立这样一种机制，或保护和/或推翻这种机制 将在完整的动物和体外细胞培养中进行分析 一种来源于小鼠骨髓和脾的可溶性抑制物 体内用PGE2处理后将进行生化提纯， 测序、克隆，并确定其作用机制。这个 前列腺素E_2的能力或介导其作用的纯化蛋白， 在致死性照射的动物模型中保护造血 和化疗，将在正常动物和肿瘤宿主中进行测试。 生长因子对提高存活率的作用将是 调查过了。人类附属细胞之间的相互关系 与细胞有关的因子，特别是CSF、PGE、IFNS和TNF 红血球的来源、释放动力学及其对红细胞生成的影响 将使用纯化的辅助细胞在体外研究骨髓生成 群体，高度浓缩的祖细胞群体，重组 前列腺素E_2的影响因素、放射免疫分析及原位杂交 技巧。转化生长因子β对人体的潜在调节作用 将使用体外克隆琼脂研究造血细胞 方法：研究方法。

This application will investigate the relationships between recombination growth factors and inhibitors in controlling myeloid progenitor cell proliferation the understanding of the interactive effects of these biomolecules is important to the ultimate clinical use of these factors for biotherapy. The interegulatory roles of recombinant murine and human growth factors G-CSF, GM-CSF, M-CSF (CSF1) Interleukin 3 and Interkeukin 1, and inhibitors, interferons alpha, beta and gamma Tumor Necrosis Factor (TNF) and prostaglandin E (PCE), in the control of murine and human hematopoietic progenitor cell proliferation will be investigated. A novel-PGE2 induced hematopoietic suppressor mechanism has been demonstrated intact animals which has broad implications to suppressed hematopoiesis in patients with Aplastic Anemia, Anemia of Chronic Disease, and Leukemia. The ability of growth factors to similarly induce such a mechanism, or protect and/or override this mechanism will be analyzed in intact animals and in in vitro cell cultures A soluble inhibitor derived from bone marrow and spleens of mice treated with PGE2 in vivo will be biochemically purified, sequenced, cloned, and its mechanism of action determined. The capacity of PGE2 or the purified protein which mediates its effect, to protect hematopoiesis, in animal models of lethal irradiation and chemotherapy, will be tested in normal animals and tumor hosts. The role of growth factors to potentiate survival will be investigated. The interrelationships between human accessory cell factors, notably CSFs, PGE, IFNs and TNF with respect to cell source, kinetics of release and effects upon Erythropoiesis and Myelopoiesis will be studied in vitro using purified accessory cell populations, high enriched progenitor cell populations, recombinant factors, radioimmunoassays for PGE2 and in situ hybridization techniques. The potential regulatory effects of TGF beta on human hematopoiesis will be investigated using in vitro clonal agar methods.