CHEMOKINE RECEPTOR EXPRESSION IN BRAIN OF MACAQUES W/ SIV ENCEPHALITIS

患有 SIV 脑炎的猕猴脑中趋化因子受体的表达

• 批准号: 6591339
• 负责人: VITO G SASSEVILLE
• 金额: $ 11.11万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6591339
• 关键词: AIDS; Mammalia; animal tissue; communicable diseases; immunology; inflammation; lymphatic system; nervous system; virus

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

虽然HIV神经入侵，神经元损伤和 随后发展HIV-1相关艾滋病痴呆症复合物（ADC） 尚不完全了解，单核细胞/巨噬细胞之间的相关性 鉴于 趋化因子和趋化因子受体的许多潜在作用可能扮演 在HIV神经病发生中，我们试图描述它们的模式 在SIV感染的HIV的SIV感染猕猴模型中的表达 脑炎我们先前证明了 猕猴大脑中的趋化因子MIP-1，MIP-1，RANTES和IP-10 在这项研究中，患有SIV脑炎的猴子，我们证明了 相应的趋化因子受体CCR3，CCR5，CXCR3以及CXCR4 IS 在这些相同组织中的血管周围浸润中表达 此外，我们在大型亚群中检测到CCR3，CCR5和CXCR4 海马和新皮层锥体神经元以及神经胶质细胞上 正常和脑脑中，这些发现表明 多种趋化因子及其受体有助于单核细胞和 SIV脑炎的淋巴细胞募集到大脑，此外， 神经元上已知的HIV/SIV共受体的表达表明A 艾滋病毒或SIV可以直接与这些相互作用的可能机制 细胞，破坏其正常的生理功能并贡献 对于ADC出版物Westmoreland SV的发病机理，Rottman JB， Williams KC，Lackner AA，Sasseville VG趋化因子受体表达 SIV的猕猴大脑中的常驻和炎症细胞 脑炎AM J Pathol，152：659-665，1998