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: 3192548
• 负责人: MICHAEL B PRYSTOWSKY
• 金额: $ 18.23万
• 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/3192548
• 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，涉及多种生物化学反应， 和所有造血元素。 T淋巴细胞扮演着不可或缺的角色 在分泌可溶性蛋白因子的炎症反应中， 淋巴因子，可以调节免疫特异性和全身性 反应的各个方面。 第一批到达感染部位的细胞 炎症是嗜中性粒细胞;巨噬细胞通常出现 几小时后，粒细胞。 克隆的T淋巴细胞是一个有效的来源 影响造血的因素。 主要的造血活性 T淋巴细胞分泌的一种因子是粒细胞-巨噬细胞 集落刺激因子（GM-CSF）。 在炎症反应期间， GM-CSF可作用于远端骨髓细胞，以增加骨髓细胞的数量。 反应性粒细胞和巨噬细胞。 该项目的一个主要目标是 将T淋巴细胞GM-CSF纯化至均一。 高度富集的 用高压离心法制备了GM-CSF， 液相色谱法 当无血清T淋巴细胞条件培养基 作为起始材料，GM-CSF将被纯化至同质。 这个项目的另一个目的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 已经表明IL 3增强了这种作用， 促红细胞生成素 然而，T淋巴细胞分泌的约10-100倍， GM-CSF高于IL 3;对骨髓净效应的分子基础 当所有三个因素都存在于生理或 病理生理学（即炎症期间）浓度未知，但 可以用纯因子检验的 此外，同质的GM-CSF将是 进行温和的蛋白水解，试图产生生物活性 肽，以确定最低结构要求， 是生物活动所必需的。 该项目的长期目标是 合成化学活性肽和结构类似物， 可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淋巴细胞在 在调节造血中起作用。