THE ROLE OF T LYMPHOCYTE FACTORS IN HEMOPOIESIS

T 淋巴细胞因子在造血中的作用

• 批准号: 3192547
• 负责人: MICHAEL B PRYSTOWSKY
• 金额: $ 15.49万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3192547
• 关键词: T lymphocyte; bioassay; colony stimulating factor; granulocyte; hematopoiesis; high performance liquid chromatography; inflammation; isoelectric point; laboratory mouse; macrophage; molecular cloning; molecular size; peptides; protein sequence; tissue /cell culture

Inflammation is a complex host response that involves several biochemical pathways and all hemopoietic elements. T lymphocytes play an integral role in inflammatory responses by secreting soluble protein factors, lymphokines, that can regulate both the immunospecific and generalized aspects of the response. The first cells to arrive at a site of inflammation are neutrophilic granulocytes; macrophages usually appear several hours after granulocytes. Cloned T lymphocytes are a potent source of factors that affect hemopoiesis. The major hemopoietically active factor that is secreted by T lymphocytes is a granulocyte-macrophage colony-stimulating factor (GM-CSF). During an inflammatory response this GM-CSF may act distally on bone marrow cells to increase the number of responding granulocytes and macrophages. A major goal of this project is to purify to homogeneity the T lymphocyte GM-CSF. A highly enriched preparation of GM-CSF has been obtained with the use of high-pressure liquid chromatography. When serum free T lymphocyte-conditioned medium is used as a starting material, the GM-CSF will be purified to homogeneity. Another aim of this project is to determine the nature of the interaction between GM-CSF, IL3 (which is also produced by T lymphocytes), and erythropoietin. It has been shown already tha IL3 potentiates the effects of erythropoietin. However, T lymphocytes secrete about 10-100-fold more GM-CSF than IL3; the molecular basis for the net effect on bone marrow cells when all three factors are present in physiological or pathophysiological (i.e. during inflammation) concentrations is unknown but testable with pure factors. In addition, homogeneous GM-CSF will be subjected to mild proteolysis in an attempt to produce biologically active peptides to determine the minimal structural requirements that are necessary for biological activity. A longterm goal of this project will be to synthesize chemically bioactive peptides and structural analogs that can be used as either stimulatory or inhibitory effectors of hemopoiesis. These studies will further our understanding of the role that T lymphocytes play in regulating hemopoiesis.

炎症是一种复杂的宿主反应，涉及几种生化反应 途径和所有的造血元素。T淋巴细胞发挥着不可或缺的作用 在炎症反应中通过分泌可溶性蛋白因子， 淋巴因子，既能调节免疫特异性又能调节全身性 回应的各个方面。第一批细胞到达一个地点 炎症是中性粒细胞；通常出现巨噬细胞 几个小时后粒细胞。克隆的T淋巴细胞是一种有效的来源 影响造血的因素。主要的造血活性物质 T淋巴细胞分泌的因子是粒细胞-巨噬细胞 集落刺激因子(GM-CSF)。在炎症反应过程中， GM-CSF可能远距离作用于骨髓细胞，增加骨髓细胞的数量。 有反应的粒细胞和巨噬细胞。这个项目的一个主要目标是 纯化纯化T淋巴细胞GM-CSF。一种高度浓缩的 用高压法制备GM-CSF 液体色谱学。当血清游离T淋巴细胞条件培养液 作为起始材料，GM-CSF将被提纯至均一。 这个项目的另一个目标是确定相互作用的性质 GM-CSF、IL-3(也由T淋巴细胞产生)和 促红细胞生成素。已有研究表明，IL3可增强这种作用。 促红细胞生成素。然而，T淋巴细胞的分泌量大约是对照组的10-100倍 GM-CSF优于IL-3；骨髓净效应的分子基础 当所有这三个因素都存在于生理或 病理生理(即在炎症期间)浓度未知，但 可用纯因素进行测试。此外，均质粒细胞集落刺激因子 经过温和的蛋白质分解，试图产生生物活性 确定满足以下要求的最低结构要求的多肽 是生物活动所必需的。该项目的长期目标将是 合成具有化学生物活性的多肽和结构类似物 用作造血的刺激或抑制效应物。 这些研究将进一步加深我们对T淋巴细胞作用的理解 在调节造血方面发挥作用。