HIV CORECEPTORS EXPRESSED BY GLIAL CELLS

描述(摘自《摘要》)：这是一份五人申请表 多年来对识别和表征神经胶质趋化因子受体的支持。 首席调查员和同事将确定已知的 趋化因子受体在小鼠星形胶质细胞和小胶质细胞上表达， 以及这些受体是否通过分析它们的功能活性 调节第二信号或趋化反应的能力。两个具体的 提出了目标。首先，研究人员将确定 通过首先观察神经胶质细胞上表达的趋化因子受体 表达已知的小鼠趋化因子受体，进而鉴定新的 使用分子技术的趋化因子受体，当这些 获得、高质量表达这些趋化因子受体蛋白 然后它们可以用来实现目标2的目标。在这个目标中， 研究人员将检测神经胶质细胞上趋化因子的活性，并观察 趋化因子受体的特异性和调控。《调查员》建议 在某些情况下，趋化因子反应发生脱敏； 研究人员也将对此进行研究。此外，《调查员》还提出 初步数据表明，在某些情况下，化学停滞(相当于 发生趋化反应)；研究人员也将对此进行研究。 为了支持申请，调查员提供了初步数据。 这证明了研究人员分离和纯化趋化因子的能力 感受器。他还表明，他在分析方面有相当多的经验 趋化因子受体结合。他已经开发出了观察星形细胞的分析方法 趋化性，并提供了令人信服的数据来证明老鼠 星形胶质细胞在趋化因子如MIP-1α和嗜酸性粒细胞趋化因子的作用下迁移 这些趋化因子受体在胶质细胞中表达。具体来说，他 已经证明在星形胶质细胞中存在CCR1和CXCR4，可能还有 CCR5也是如此。虽然星形胶质细胞有CXCR4，但它们似乎没有 对CXCR4配体刺激后的趋化反应 趋化因子SDF-1。

DESCRIPTION (adapted from the Abstract): This is an application for five years of support to identify and characterize glial chemokine receptors. The Principal Investigator and associates will determine which of the known chemokine receptors are expressed on murine astrocytes and microglial cells, and whether these receptors are functionally active by assaying for their ability to mediate second signals or chemotactic responses. Two specific aims are proposed. In the first, the researchers will identify the chemokine receptors that are expressed on glial cells by first looking at the expression of known murine chemokine receptors, then identify novel chemokine receptors using molecular techniques, and, when those are obtained, express those chemokine receptor proteins in high quantities such that they can then be used to accomplish the goals of Aim #2. In this aim, the researchers will examine the activity of chemokines on glia and look at chemokine receptor specificity and modulation. The Investigator proposes that in some instances a desensitization of chemokine responses occurs; the researchers will examine this, as well. Further, the Investigator offers preliminary data that suggest that in some instances a chemostasis (rather than a chemotactic) response occurs; the researchers will study this, also. In support of the application, the Investigator includes preliminary data that demonstrate the researchers' ability to isolate and purify chemokine receptors. He shows, also, that he has considerable experience in analyzing chemokine receptor binding. He has developed assays to look at astrocytic chemotaxis and presents convincing data that demonstrate that mouse astrocytes migrate in response to chemokines like MIP-1 alpha and eotaxin and that those chemokine receptors are expressed in glia. Specifically, he has shown the presence of CCR1 and CXCR4 in astrocytes and, possibly, of CCR5, as well. Although astrocytes have CXCR4, they do not appear to respond with chemotaxis after stimulation with the CXCR4 ligand, the chemokine SDF-1.