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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 最近的研究表明，神经精神障碍与艾滋病毒/SIV感染之间存在联系。大多数证据表明，单核/巨噬细胞是中枢神经系统内感染的主要细胞类型，它们与中枢神经系统炎症和神经系统疾病有关。P物质(SP)是一种多效性神经肽，通过与其同源受体神经激肽1受体(NK1-R)相互作用，参与炎症、抑郁和免疫调节，由单核/巨噬细胞产生。虽然NK1-R在神经元上的存在是众所周知的，但它在免疫系统细胞如单核/巨噬细胞上的作用才刚刚开始出现。因此，我们研究了SP和NK1-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NK1-R在SIVE皮损中的表达显著增加。在这些病变中，顶噬细胞是表达NK1-R的主要细胞。SIV感染的巨噬细胞均表达NK1-R。此外，我们还研究了SP作为单核细胞活化和趋化的促炎介质的功能作用。单核细胞经SP处理后，细胞表面CCR5和NK1-R的表达发生了剂量依赖性的变化。SP处理可增强SP和CCL5介导的趋化作用。综上所述，这些观察结果表明，SP和NK1-R在SIV感染巨噬细胞和SIVE病变的发生发展中起重要作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. acrophages 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.