ALCOHOL, HIV, AND ENDOTHELIUM/MONOCYTE INTERACTIONS

酒精、HIV 和内皮/单核细胞相互作用

• 批准号: 2389934
• 负责人: John D Shanley
• 金额: $ 17.71万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2389934
• 关键词: HIV infections; acetaldehyde; blood brain barrier; brain; capillary; cell adhesion; cell free system; cell migration; cytokine; ethanol; human tissue; immunity; monocyte; tissue /cell culture; vascular endothelium; virus infection mechanism; virus replication

Alcohol abuse, a major health problem in the US, is known to alter host immunity and suppress host defenses to a number of infectious agents. Ethanol is a major problem among the populations affected by HIV. However, the effects of ethanol and its metabolites on the pathogenesis of HIV infection are largely unexplored. Monocytes and macrophages are now known to be major reservoirs of HIV and it has been postulated that these cells are responsible for dissemination of HIV throughout the body, including the central nervous system. The egress of monocytes into tissues require these cells to transverse the microvessel endothelial cells that line the vasculature. In the central nervous system, this occurs across brain microvessel endothelial cells (BMEC), which constitute the blood brain barrier (BBB). Ethanol has been shown to alter the properties of both monocytes and endothelial cells. Alcohol and its metabolites may thus alter the interaction of HIV with monocytes and endothelial cells or the interaction of monocytes and endothelial cells with each other. These effects are likely to effect the pathogenesis of HIV into host tissues. Using an in vitro model of monocyte:microvessel endothelial cell interaction, this proposal will examine the effects of ethanol and its major metabolite, acetaldehyde, on the susceptibility of monocytes and endothelial cells to HIV. Because of the importance of HIV in the CNS, we will focus on the brain microvessel endothelial cells. It will also examine the effects of ethanol on the adherence and transmigration of monocytes across the endothelial lining. The broad objective of this proposal is to test the hypothesis that ethanol and/or its metabolite, acetaldehyde, alter the susceptibility of monocytes and/or microvessel endothelial cells to HIV infection and replication. Further, ethanol and its metabolites modify the interaction of normal and HIV infected monocytes with microvessel endothelial cells, thus affecting monocyte adherence and transmigration. These effects may suppress the inflammatory response or facilitate entry of HIV into tissues, thus contributing to the progression of HIV infection.

酗酒是美国的一个主要健康问题， 免疫力和抑制宿主对许多传染性病原体的防御。 乙醇是受艾滋病毒影响的人群中的一个主要问题。 然而，在这方面， 乙醇及其代谢产物对HIV发病机制的影响 感染在很大程度上未被探索。 现在已知单核细胞和巨噬细胞 是HIV病毒的主要宿主， 负责传播艾滋病毒在整个身体，包括 中枢神经系统 单核细胞进入组织需要这些 细胞穿过微血管内皮细胞， 脉管系统 在中枢神经系统中，这发生在大脑中， 微血管内皮细胞（BMEC），构成血脑 屏障（BBB）。 乙醇已被证明可以改变两者的性质 单核细胞和内皮细胞。 因此，酒精及其代谢产物可能 改变艾滋病毒与单核细胞和内皮细胞的相互作用或 单核细胞和内皮细胞相互作用。 这些 作用可能影响HIV进入宿主组织的发病机制。 应用单核细胞-微血管内皮细胞体外模型 相互作用，这项建议将研究乙醇及其 主要代谢产物乙醛对单核细胞易感性的影响， 内皮细胞感染艾滋病毒。 由于HIV在CNS中的重要性，我们 将集中于脑微血管内皮细胞。 它还将 检查乙醇对粘附和迁移的影响， 单核细胞穿过内皮细胞。 其主要目标是 建议是检验乙醇和/或其代谢物， 乙醛，改变单核细胞和/或微血管的易感性 内皮细胞对HIV感染和复制的影响。 此外，乙醇和 它的代谢物改变正常和HIV感染的单核细胞的相互作用 与微血管内皮细胞，从而影响单核细胞粘附， 轮回 这些作用可能抑制炎症反应， 促进HIV进入组织，从而促进进展 艾滋病毒感染。