ALCOHOL, HIV, AND ENDOTHELIUM/MONOCYTE INTERACTIONS

酗酒是美国的一个主要健康问题，众所周知，酗酒会改变宿主 免疫和抑制宿主对一些感染性病原体的防御。 在感染艾滋病毒的人群中，乙醇是一个主要问题。然而， 乙醇及其代谢产物在HIV致病机制中的作用 感染在很大程度上是未知的。单核细胞和巨噬细胞现在是已知的 是HIV的主要宿主，据推测，这些细胞 负责艾滋病毒在全身的传播，包括 中枢神经系统。单核细胞进入组织需要这些 细胞横穿排列在血管内皮细胞 脉管系统。在中枢神经系统中，这种情况发生在整个大脑中 构成血脑的微血管内皮细胞(BMEC) 屏障(BBB)。乙醇已被证明可以改变这两种物质的性质 单核细胞和内皮细胞。酒精及其代谢物可能因此 改变HIV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 这些影响可能会影响艾滋病毒进入宿主组织的致病机制。 使用单核细胞的体外模型：微血管内皮细胞 互动，这项建议将审查乙醇和其影响 主要代谢产物乙醛对单核细胞易感性的影响 血管内皮细胞感染HIV病毒。由于艾滋病毒在中枢神经系统的重要性，我们 将重点放在脑微血管内皮细胞上。它还将 检测乙醇对细胞黏附和移行的影响 单核细胞横跨内皮细胞层。这样做的总体目标是 建议测试乙醇和/或其代谢物的假设， 乙醛，改变单核细胞和/或微血管的敏感性 内皮细胞对HIV的感染和复制。此外，乙醇和 其代谢产物改变正常单核细胞和HIV感染单核细胞的相互作用 与微血管内皮细胞结合，从而影响单核细胞的黏附和 轮回。这些作用可能会抑制炎症反应或 促进艾滋病毒进入组织，从而促进进展 艾滋病毒感染的可能性。

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.