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 大脑中的浸润物和神经系统疾病的存在 趋化因子和趋化因子受体可能发挥的多种潜在作用 在HIV神经发病机制中，我们试图描述他们的模式 HIV在SIV感染恒河猴模型中的表达 脑炎我们之前发现了高表达的脑脊液 猕猴脑内趋化因子MIP-1‘、MIP-1、RANTES和IP-10的表达 在这项研究中，我们证明了SIV脑炎的猴子 相应的趋化因子受体CCR3、CCR5、CXCR3和CXCR4是 在血管周围浸润性组织中的表达 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 无论是正常人还是脑炎患者，这些发现都表明 多种趋化因子及其受体促进单核细胞和 SIV脑炎的淋巴细胞向脑内募集 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 对ADC出版物Westmoland SV，Rottman JB， Williams KC、Lackner AA、Sasseville VG趋化因子受体表达 SIV对猕猴脑内滞留细胞和炎性细胞的研究 流行性乙型脑炎，152：659-665,1998

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-1`, MIP-1 , 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 encephaliti c b rain 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 Publications Westmoreland SV, Rottman JB, Williams KC, Lackner AA, Sasseville VG Chemokine receptor expression on resident and inflammatory cells in the brain of macaques with SIV encephalitis Am J Pathol, 152:659-665, 1998