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（改编自申请人的摘要）几条证据支持这样的概念：重要的改变肺实质中存在大量 HIV- 在发展为公认的血清阳性个体之前肺部并发症。虽然这些疾病的发病机制异常现象仍不清楚，最近的证据表明 HIV 相关淋巴细胞性肺泡炎的重要作用和关键肺泡淋巴细胞-肺泡巨噬细胞相互作用。的目标目前的项目是通过严格检查来扩展这些观察结果淋巴细胞性肺泡炎的重要性肺损伤的生理和形态学证据以及关于肺泡巨噬细胞细胞因子产生的失调。为了实现这一目标，将审查以下具体目标目标。具体目标 1 解决了这个问题：体内存在吗？ HIV 相关淋巴细胞性肺泡炎的关键决定因素实质肺损伤和促炎细胞因子上调？这目标将前瞻性地描述淋巴细胞的重要性肺泡炎的生理、放射学和形态测量肺实质损伤以及体内损伤的证据促炎细胞因子诱导。具体目标2中的问题地址：体外是否存在肺泡细胞毒性 T 淋巴细胞 TNF α 和 IL-1 产生的重要调节因子肺泡巨噬细胞的β作用？该目标将研究基本机制促炎细胞因子的调节，将主要集中于 CD8+细胞毒性淋巴细胞对IL-β加工和释放的影响由肺泡巨噬细胞。因为这项研究的意义在于是最常见的炎症事件之一 HIV 的肺泡环境，它可能会极大地增进对 HIV 的认识相关肺部疾病。也许更重要的是，它专注于角色肺泡淋巴细胞作为协调的核心角色与肺泡相互作用造成肺实质损伤巨噬细胞。因此，该项目提供了一个机会阐明肺损伤的新机制并更好地理解对监管具有潜在根本重要性的因素炎。