CHEMOKINE RECEPTOR EXPRESSION IN BRAIN OF MACAQUES W/ SIV ENCEPHALITIS

尽管HIV神经侵袭、神经元损伤和 HIV-1相关的艾滋病痴呆综合征(ADC)的后续发展 还没有完全了解，单核/巨噬细胞之间的相关性 渗透到大脑中，存在神经疾病。根据…… 趋化因子和趋化因子受体可能的多种潜在作用 在HIV神经发病机制中，我们试图描述它们的模式 HIV在SIV感染恒河猴模型中的表达 脑炎。我们之前证明了该基因的高表达。 猕猴脑内趋化因子MIP-1a、MIP-1b、RANTES和IP-10的表达 患有SIV脑炎的猴子。在这项研究中，我们证明了 相应的趋化因子受体CCR3、CCR5、CXCR3和CXCR4是 在这些相同的组织中表达在血管周围的浸润物中。在……里面 此外，我们检测到CCR3、CCR5和CXCR4在大型 大鼠海马和新皮质锥体神经元及神经胶质细胞 无论是正常大脑还是脑炎大脑。这些发现表明， 多种趋化因子及其受体促进单核细胞和 SIV脑炎患者的淋巴细胞向脑内募集。此外， 已知的HIV/SIV协同受体在神经元上的表达表明 HIV或SIV可以直接与这些病毒相互作用的可能机制 细胞，扰乱它们的正常生理功能，并导致 与ADC的发病机制有关。

Although the mechanisms of HIV neuroinvasion, neuronal injury, and subsequent development of HIV-1-associated AIDS dementia complex (ADC) are not fully understood, a correlation between monocyte/macrophage infiltrates in the brain and neurologic disease exists. In light of the many potential roles that chemokines and chemokine receptors may play in HIV neuropathogenesis, we sought to describe their pattern of expression in the SIV-infected rhesus macaque model of HIV encephalitis. We previously demonstrated elevated expression of the chemokines MIP-1a, MIP-1b, RANTES, and IP-10 in brain of macaque monkeys with SIV encephalitis. In this study, we demonstrate that the corresponding chemokine receptors CCR3, CCR5, CXCR3 and also CXCR4 are expressed in perivascular infiltrates in these same tissues. In addition, we detected CCR3, CCR5, and CXCR4 on subpopulations of large hippocampal and neocortical pyramidal neurons and on glial cells in both normal and encephalitic brain. These findings suggest that multiple chemokines and their receptors contribute to monocyte and lymphocyte recruitment to the brain in SIV encephalitis. Furthermore, the expression of known HIV/SIV coreceptors on neurons suggests a possible mechanism whereby HIV or SIV can directly interact with these cells, disrupting their normal physiologic function and contributing to the pathogenesis of ADC.