LYMPHOCYTIC ALVEOLITIS, IL 1B REGULATION AND LUNG INJURY

淋巴细胞性肺泡炎、IL 1B 调节和肺损伤

基本信息

批准号：
2750440
负责人：
Mark Damian Wewers
金额：
$ 26.2万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-08-01 至 1999-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2750440
关键词：
CD8 molecule allergic pneumonitis alveolar macrophages cytotoxic T lymphocyte genetic regulation human immunodeficiency virus interleukin 1 lung injury morphology tumor necrosis factor alpha

项目摘要

DESCRIPTION (Adapted from the applicant's abstract) Several lines of evidence support the concept that important alterations in the pulmonary parenchyma occur in a substantial number of HIV- seropositive individuals prior to the development of recognized pulmonary complications. Although the pathogenesis of these abnormalities remains obscure, recent evidence has suggested an important role for an HIV-associated lymphocytic alveolitis and critical alveolar lymphocyte-alveolar macrophage interactions. The goal of the present project is to extend these observations by rigorously examining the significance of a lymphocytic alveolitis both with respect to physiologic and morphologic evidence of lung injury as well as with respect to dysregulation of cytokine production by alveolar macrophages. The following specific aims will be examined in an effort to reach this goal. Specific Aim 1 addresses this question: Is the in vivo presence of an HIV-associated lymphocytic alveolitis a critical determinant of parenchymal lung injury and proinflammatory cytokine upregulation? This aim will prospectively delineate the importance of a lymphocytic alveolitis with respect to physiologic, radiographic, and morphometric evidence of parenchymal lung damage as well as with respect to in vivo proinflammatory cytokine induction. The question in Specific Aim 2 addresses: Is the in vitro presence of alveolar cytoxic T- lymphocytes an important regulatory factor in the production of TNF alpha and IL-1 beta by alveolar macrophages? This aim will examine basic mechanisms of proinflammatory cytokine regulation and will focus primarily on the effects of CD8+ cytotoxic lymphocytes on IL-beta processing and release by alveolar macrophages. Because this study addresses the significance of one of the most common of the inflammatory events occurring in the alveolar environment in HIV, it may greatly advance knowledge of HIV- related lung disease. Perhaps more importantly, it focuses on the role of the alveolar lymphocyte as a central player in orchestrating pulmonary parenchymal damage through interactions with alveolar macrophages. As such, this project represents an opportunity to elucidate novel mechanisms of lung injury and to better understand factors of potentially fundamental importance to the regulation of inflammation.

描述（根据申请人的摘要改编）几条证据支持重要改变的概念在肺实质中发生大量HIV- 在公认的发展之前，血清反应阳性的个体肺并发症。尽管这些发病机理异常仍然晦涩难懂，最近的证据表明与HIV相关的淋巴细胞肺泡炎和关键的重要作用肺泡淋巴细胞 - 肺泡巨噬细胞相互作用。目标的目标目前的项目是通过严格检查来扩展这些观察结果相对于肺损伤的生理和形态学证据关于肺泡巨噬细胞产生细胞因子的失调。将检查以下具体目标以实现这一目标目标。具体目标1解决了这个问题：是体内存在与HIV相关的淋巴细胞肺泡炎的关键决定因素实质肺损伤和促炎细胞因子上调？这 AIM将前瞻性地描述淋巴细胞的重要性关于生理，射线照相和形态计量学的肺泡炎实质性肺损伤以及体内的证据促炎细胞因子诱导。特定目标中的问题2 地址：肺泡细胞毒性T-淋巴细胞的体外存在 TNF alpha和IL-1的生产的重要调节因素肺泡巨噬细胞的β？这个目标将检查的基本机制促炎性细胞因子调节，主要关注 CD8+细胞毒性淋巴细胞对IL-BETA加工和释放的影响通过肺泡巨噬细胞。因为这项研究解决了重要性其中最常见的炎症事件发生在艾滋病毒中的肺泡环境，它可能会大大提高对艾滋病毒的了解相关肺部疾病。也许更重要的是，它专注于角色肺泡淋巴细胞作为策划的中心参与者通过与牙槽相互作用的肺实质损伤巨噬细胞。因此，这个项目代表了一个机会阐明肺损伤的新型机制，以更好地理解对监管的潜在重要性的因素炎。