NEUROKININ-1 RECEPTOR EXPRESSION IN THE BRAINS OF SIV-INFECTED RHESUS MACAQUES

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 最近的研究表明，神经精神疾病和艾滋病毒/SIV感染之间的联系。 大多数证据表明，单核细胞/巨噬细胞是CNS内感染的主要细胞类型，它们导致CNS炎症和神经系统疾病。 P物质（SP）是由单核细胞/巨噬细胞产生的一种多效神经肽，其通过与其同源受体神经激肽1受体（NK 1-R）相互作用而参与炎症、抑郁和免疫调节。 虽然NK 1-R在神经元上的存在是众所周知的，但其在免疫系统细胞如单核细胞/巨噬细胞上的作用才刚刚开始出现。 因此，我们研究了SP和NK 1-R的表达及其与SIVE病变和SIV感染细胞的关系。这些研究表明，SP和NK 1-R的表达在SIVE病变中显著增加。巨噬细胞是这些病变中表达NK 1-R的主要细胞。 所有SIV感染的巨噬细胞均表达NK 1-R。 此外，我们研究了SP作为单核细胞活化和趋化性的促炎介质的功能作用。 SP处理单核细胞引起细胞表面CCR 5和NK 1-R表达的变化，呈剂量依赖性。 用SP处理增强SP和CCL 5介导的趋化性。 总之，这些观察结果表明，SP和NK 1-R的作用是重要的SIV感染的巨噬细胞和SIVE病变的发展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Recent studies suggest a link between neuropsychiatric disorders and HIV/SIV infection. Most evidence indicates monocytes/macrophages are the primary cell type infected within the CNS and that they contribute to CNS inflammation and neurologic disease. Substance P (SP), a pleotropic neuropeptide implicated in inflammation, depression and immune modulation via interaction with its cognate receptor, the neurokinin 1 receptor (NK1-R), is produced by monocyte/macrophages. While the presence of NK1-R on neurons is well known, its role on cells of the immune system such as monocyte/macrophages is just beginning to emerge. Therefore, we have examined the expression of SP and NK1-R and their relationship to SIVE lesions and SIV-infected cells. These studies demonstrated that the expression of SP and NK1-R is significantly increased in SIVE lesions. Macrophages are the principal cell expressing NK1-R in these lesions. All of the SIV-infected macrophages expressed NK1-R. Additionally, we examined the functional role of SP as a proinflammatory mediator of monocyte activation and chemotaxis. The treatment of monocytes with SP elicited changes in cell-surface expression for CCR5 and NK1-R in a dose-dependent manner. Treatment with SP enhanced both SP and CCL5 mediated chemotaxis. Taken together, these observations suggest that the role of SP and NK1-R are important in SIV infection of macrophages and the development of SIVE lesions.