TISSUE FACTOR AS A SURROGATE MARKER OF HIV

单核细胞-巨噬细胞是免疫系统的重要调节细胞。 在感染期间，巨噬细胞的调节发生了变化；然而， 目前还没有好的系统来评估巨噬细胞的功能 可以在艾滋病毒相关疾病的发展过程中进行监测。至 研究在急性胰腺炎期间巨噬细胞功能的评估机制 感染，我已经评估了细胞因子产生的调节，通过 从感染艾滋病毒的人身上获得的巨噬细胞。在此期间 研究发现，稳定的淋巴因子水平会刺激 有症状的HIV患者组织因子(TF)mRNA表达降低 感染，并且存在Tf功能减弱的连续体 患有无症状疾病、ARC和艾滋病的患者。相比之下，单核细胞 来自艾滋病和ARC的患者继续表现出显著的肿瘤反应 肿瘤坏死因子和白介素1-β。基于这些观察，我们 假设Tf可能是一个很好的替代标记物 疾病的进展，并可作为病情好转的指标 接受有益治疗的个体的免疫功能。在这 建议，我打算监测接受Tf治疗的患者的诱导Tf水平 UCSD ACTU正在研究的特定ACTG方案的治疗。 这些研究中的患者将在一年内以固定的间隔进行监测 本建议书的年度期限。收集的单核细胞将被刺激 LPS孵育4小时，提取RNA，并冷冻一份细胞的Tf RNA和 每个个体的蛋白质水平将同时进行检测。 此外，由于体外信号由T细胞提供给单核细胞， 单核细胞受单核细胞促凝血剂诱导因子刺激 (MPIF)以确定MPIF诱导的转铁蛋白是否是更敏感的 单核细胞功能优于内毒素诱导的转铁蛋白。因此，内毒素-MPIF的效用- 诱导的转铁蛋白将被评估为单核细胞功能和 与参与ACTG治疗的患者的临床结果进行比较 协议。

Monocytes-macrophages are important regulatory cell of the immune system. During an infection, macrophages show altered regulation; however, presently no good system exists for evaluation of macrophage function that can be monitored during the course of HIV-related disease progression. To examine mechanisms for evaluation of macrophage function during an infection, I have evaluated the regulation of cytokine production by macrophages obtained from individuals infected with HIV. During these studies, I have found that steady state levels of lymphokine stimulated tissue factor (TF) mRNA are decreased in individuals with symptomatic HIV infection and that there is a continuum of diminished TF function in patients with asymptomatic disease, ARC, and AIDS. In contrast, monocytes from AIDS and ARC patients continue to show notable responses of tumor necrosis factor and interleukin 1-beta. Based on these observations we hypothesize that TF may be an excellent surrogate marker for monitoring the progression of the disease and may be useful as an indicator of improved immunologic function in individuals receiving beneficial therapy. In this proposal, I intend to monitor induced levels of TF in patients receiving treatment in specific ACTG protocols under study at the UCSD ACTU. Patients in these studies will be monitored at fixed intervals over the one year period of this proposal. Monocytes collected will be stimulated with LPS for 4 hrs, RNA extracted, and an aliquot of cells frozen TF RNA and protein levels form each individual will be assayed simultaneously. Additionally, since in vitro signals are provided to monocytes by T-cells, monocytes will be stimulated by monocyte procoagulant inducing factor (MPIF) to determine if MPIF induced TF is a more sensitive marker of monocyte function than LPS-induced TF. Thus, the utility of both LPS-MPIF- induced TF will be evaluated as surrogate markers for monocyte function and compared with the clinical outcomes in patients involved in ACTG treatment protocols.