THE ROLE OF T LYMPHOCYTE FACTORS IN HEMOPOIESIS
THE ROLE OF T LYMPHOCYTE FACTORS IN HEMOPOIESIS
批准号:
3192551
负责人:
MICHAEL B PRYSTOWSKY
金额:
$13.63万
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-04-01 至 1993-03-31
中文摘要
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。
英文摘要
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.
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