HIV CORECEPTORS EXPRESSED BY GLIAL CELLS

描述（改编自摘要）：这是一个五个应用程序 多年的支持，以确定和表征胶质细胞趋化因子受体。 主要研究者和同事将确定哪些已知的 趋化因子受体在鼠星形胶质细胞和小胶质细胞上表达， 以及这些受体是否具有功能活性， 介导第二信号或趋化反应的能力。 两个具体 提出了目标。 首先，研究人员将确定 首先通过观察在神经胶质细胞上表达的趋化因子受体， 表达已知鼠趋化因子受体，然后鉴定新的 趋化因子受体的分子技术，当这些 大量表达那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。 在这一目标下， 研究人员将检测胶质细胞上趋化因子的活性， 趋化因子受体特异性和调节。 研究者建议 在某些情况下，发生趋化因子反应的脱敏; 研究人员也将对此进行研究。 此外，研究人员提供 初步数据表明，在某些情况下， 比趋化性）反应发生;研究人员也将研究这一点。 为了支持申请，研究者包括初步数据 这证明了研究人员分离和纯化趋化因子的能力， 受体。 他还表明，他在分析方面有相当丰富的经验， 趋化因子受体结合。 他开发了一种检测星形胶质细胞 趋化性，并提出了令人信服的数据，表明小鼠 星形胶质细胞响应趋化因子如MIP-1 α和嗜酸性粒细胞趋化因子迁移 这些趋化因子受体在神经胶质细胞中表达。 他特别 已经表明星形胶质细胞中存在CCR 1和CXCR 4，并且可能存在CCR 1和CXCR 4。 CCR 5也是。 虽然星形胶质细胞具有CXCR 4，但它们似乎不具有CXCR 4。 在用CXCR 4配体刺激后， 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.