Alveolar macrophage proteomics in HIV-induced emphysema

描述（由申请人提供）： 有证据表明，艾滋病毒血清阳性吸烟者患肺气肿的风险增加。了解这一现象的自然史对HIV背景下的肺部疾病具有重要意义。此外，描绘重要的分子机制，负责这一加速过程可能有广泛的相关性肺气肿的发病机制。为了更好地了解艾滋病毒相关的肺气肿，目前的建议旨在解决两个具体目标：具体目标1。描述HAART时代HIV相关肺气肿的自然史。在这个目标中，我们将测试的假设，实质肺损伤是衰减在HAART时代。我们还将研究一组具有显著气体交换改变的患者的生理异常进展。具体目标2。在这个目标中，我们将比较从HIV血清阳性的吸烟者和没有肺气肿的肺泡巨噬细胞的蛋白质组。该项目的成功完成将使我们能够进一步阐明艾滋病毒血清阳性人群中吸烟相关肺损伤的重要性。更重要的是，本提案中提出的研究将提供一个独特的机会来检查早期肺气肿进展的相关机制。

DESCRIPTION (provided by applicant): Evidence exists that HIV-seropositve smokers are at increased risk for developing pulmonary emphysema. Understanding the natural history of this phenomenon has important implications regarding lung disease in the setting of HIV. Furthermore, delineating important molecular mechanisms responsible for this accelerated process may have broad relevance regarding emphysema pathogenesis. In order to gain better insight into HIV- associated emphysema the current proposal seeks to address two specific aims: Specific Aim 1. To delineate the natural history of HIV-associated emphysema in the HAART era. In this aim we will test the hypothesis that parenchymal lung damage is attenuated in the HAART era. We will also examine the progression of physiologic abnormalities among a well characterized group with prominent gas exchange alterations. Specific Aim 2. In this aim we will compare the proteomes of alveolar macrophages obtained from HIV-seropositive smokers with and without emphysema. Successful completion of this project will enable us to further delineate the importance of smoking related lung damage occurring in the HIV-seropositive population. More importantly, the research proposed in this proposal will provide a unique opportunity to examine relevant mechanisms underlying the progression of early emphysema.