REGULATION OF MYELOPOIESIS: SUPPRESSOR FACTOR SYNERGISM

大鼠造血干/祖细胞增殖的调控 VIVE很有可能是由 刺激生长和抑制生长的分子。我们已经定义了 表征了纯化的天然分子和重组分子的影响 如酸性异铁蛋白、干扰素γ、α和β、E 前列腺素、肿瘤坏死因子正常与异常的关系 造血术。对我们非常感兴趣，而且可能非常重要 以及与理解生理调节的相关性 体内造血细胞的增殖及其异常 白血病和相关血液疾病的调控是最近的 我们和其他人的研究发现，某些分子可以相互协同 另一些在体外，因此注意到的影响比相加要大得多。 我们建议研究分子间的协同作用现象 体外和体内。我们的目标是进一步和更准确地评估 单独操作和交互，以及与具有良好特征的和 纯化的天然或重组酸性异铁蛋白、干扰素-γ和 -α、前列腺素E_1或E_2和肿瘤坏死因子对人卵巢癌细胞生长的影响 新鲜原代正常人和小鼠髓系细胞的体外培养 白血病和相关疾病的患者，以及已建立的人类 体外培养髓系白血病细胞株。我们的目标是研究这些 使用纯分子和纯化的群体的分子-细胞相互作用 通过生物物理和免疫程序分离的靶细胞，在 血清的存在和缺失。体外研究将包括一项分析 用集落形成细胞分析法检测这些分子的活性 (CFU-GM、BFU-E、CFU-GEMM、S-细胞)，这些细胞的受体结合能力 分子，以及这些分子对基因表达的影响 原癌基因。我们还建议评估单独和合并的 这些分子在反弹骨髓生成小鼠体内的作用， 在未经治疗的小鼠和感染Friend Viruis复合体的小鼠中。我们 相信建议的研究将会加深我们对 这些分子的相关性和协同作用的概念适用于 正常和不正常的调节。

The control of proliferation of hematopoietic stem and progenitor cells in vivo is most likely the end result of the production and action of growth-stimulating and growth-suppressing molecules. We have defined and characterized the influence of purified natural and recombinant molecules such as acidic isoferritins, the interferons gamma, alpha and beta, the E type prostaglandins, and tumor necrosis factor on normal and abnormal hematopoiesis. Of much interest to us, and potentially of great importance and relevance to an understanding of the physiological regulation of hematopoietic cell proliferation in vivo and of abnormalities in this regulation during leukemia and related blood disorders is the recent findings by us and others that certain molecules can synergise with each other in vitro so that the effects noted are much greater than additive. We propose to investigate the phenomenon of synergism between molecules in vitro and in vivo. Our aims are to evaluate further and more precisely the actions and interactions alone and in combination of well-characterized and purified natural or recombinant acidic isoferritins, interferons-gamma and -alpha, prostaglandin E1 or E2 and tumor necrosis factor on the growth in vitro of fresh primary normal human and murine myeloid cells, on cells from patients with leukemia and related disorders, and on established human myeloid leukemia cell lines in vitro. Our goal is to study these molecule-cell interactions using pure molecules and purified populations of target cells, isolated by biophysical and immunological procedures, in the presence and absence of serum. Studies in vitro will include an analysis of the activity of these molecules using colony forming cell assays (CFU-GM, BFU-E, CFU-GEMM, S-cells), the receptor-binding capacity of these molecules, and effects of these molecules on the expression of proto-oncogenes. We also propose to evaluate the separate and combined actions of these molecules in vivo in mice undergoing rebound myelopoiesis, in untreated mice, and in mice infected with the Friend Viruis Complex. We believe that the studies proposed will increase our understanding of the relevance of these molecules and the concept of synergism as it applies to normal and abnormal regulation.