MATH MODEL OF EXTRAVASATION OF LEUKOCYTES IN SIV INFECTION IN RHESUS MACAQUES

恒河猴 SIV 感染白细胞外渗的数学模型

• 批准号: 7562326
• 负责人: XAVIER ALVAREZ
• 金额: $ 7.16万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562326
• 关键词: Acquired Immunodeficiency Syndrome; Blood - brain barrier anatomy; Brain; Cell Count; Cells; Computer Retrieval of Information on Scientific Projects Database; Confocal Microscopy; Detection; Disease; Extravasation; Funding; Grant; HIV; Human; Imagery; Immunohistochemistry; Infection; Institution; Interleukin-6; Lead; Leukocyte Trafficking; Leukocytes; Macaca mulatta; Modeling; Neuropathogenesis; Pathogenesis; Population; Prevention; Protocols documentation; Research; Research Personnel; Resources; Signal Transduction; Source; System; T-Lymphocyte; Techniques; United States National Institutes of Health; Virus; cytokine; macrophage; mathematical model; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The trafficking of leukocytes through the blood brain barrier in the presence of disease, as in the case of human AIDS, is too complicated to understand intuitively. We have developed a protocol utilizing the techniques of immunohistochemistry and confocal microscopy to achieve simultaneous detection and visualization of cell populations and signals involved in the neuropathogenesis of AIDS. However, the number of cells and cytokines produced during neuroinvasion are far too numerous to accurately gain an understanding of their activities in response to infection. Therefore, we have begun developing a mathematical model to track the leukocyte extravasation at the BBB in order to accommodate the major activities of the cytokines and to establish a sequence in which these cells arrive to deliver the virus into the brain. Although the pathogenesis is still unclear, we propose that SIV-infected macrophages producing IL-6 are the first cells to arrive, followed by T-cells producing IL-6 and IFN-¿, and finally macrophages producing TNF-¿ or ¿. This study discusses the techniques carried out to develop this model and attempts to qualitatively examine this system of infection to ultimately propose points of interference that could lead to advancements in the treatment of HIV and possible prevention of such infections into the brain.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在疾病存在的情况下，白细胞通过血脑屏障的运输，就像人类艾滋病的情况一样，太复杂了，无法直观地理解。我们开发了一种方案，利用免疫组织化学和共聚焦显微镜技术，实现了对参与艾滋病神经发病机制的细胞群体和信号的同时检测和可视化。然而，在神经侵袭过程中产生的细胞和细胞因子的数量太多，无法准确地了解它们在应对感染时的活动。因此，我们已经开始开发一个数学模型来跟踪血脑屏障的白细胞外溢，以适应细胞因子的主要活动，并建立这些细胞到达将病毒传递到大脑的序列。虽然发病机制尚不清楚，但我们认为SIV感染的巨噬细胞产生IL-6是第一批到达的细胞，其次是产生IL-6和干扰素的T细胞，最后是产生肿瘤坏死因子-β的巨噬细胞。这项研究讨论了开发这一模型所采用的技术，并试图对这一感染系统进行定性检查，以最终提出可能导致艾滋病毒治疗进步和可能防止此类感染进入大脑的干扰点。