PSEUDOMONAS PRODUCTS, OXYGEN RADICALS, AND LUNG INJURY
假单胞菌产物、氧自由基和肺损伤
基本信息
- 批准号:6124279
- 负责人:
- 金额:$ 22.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1993
- 资助国家:美国
- 起止时间:1993-12-01 至 2003-11-30
- 项目状态:已结题
- 来源:
- 关键词:Pseudomonas aeruginosa bacterial cytopathogenic effect bacterial pigment bacterial toxins cell transplantation cellular pathology cystic fibrosis cytotoxicity free radical oxygen interleukin 8 lung injury microorganism culture oxidative stress protein purification respiratory epithelium tissue /cell culture
项目摘要
Pseudomonas aeruginosa causes acute nosocomial pneumonia as well as
chronic lung infections in cystic fibrosis patients. The mechanisms
responsible for the resulting lung injury remain unclear. Formation of
oxidant species such as superoxide and hydrogen peroxide are associated
with many forms of lung injury. During the initial funding period of this
program, we obtained evidence that three compounds actively secreted by P.
aeruginosa damage pulmonary epithelial and endothelial cells via oxidant
production. In the next funding period we will define the cellular
mechanisms of action of redox cycling. This results in superoxide and
hydrogen peroxide generation. Pyocyanin causes a host of deleterious
effects on cellular functions both in vitro and in vivo. In spite of this,
there is only limited data on the cellular events by cells. Furthermore,
the site(s), mechanism(s), and nature of the oxidants produced by
pyocyanin, as well as the cellular targets are also poorly understood. We
hypothesize that the complex series of effects mediated by pyocyanin occur
through its ability to induce site specific oxidant production which leads
to the disruption of cellular energy generation and activation of oxidant
sensitive signaling pathways. To test this hypothesis three specific aims
will be accomplished. Aim 1 is to identify the mechanism(s) of epithelial
cell acquisition, cellular trafficking, and metabolism of pyocyanin under
in vitro conditions. Aim 2 is to determine how pyocyanin deplete
epithelial cells of ATP and cAMP by defining the effects of pyocyanin on
oxidative phosphorylation and glycolysis. This aim will also address if
pyocyanin acts on oxidant-regulated signaling pathways, IL-8 expression
will serve as a model system. The first two aims will use an in vitro
system of polarized epithelial cell monolayers using normal and CF cells.
Aim 3 will examine the extent to which the in vitro effects of pyocyanin
are observed occur under in vivo conditions. This work will focus on IL-8
release and utilize xenografts of human respiratory epithelial cells in
SCID mice. These studies will use state of the art technique of cell
biology and oxidant chemistry to define novel and previously unexplored
mechanisms whereby P. aeruginosa may contribute to acute and/or chronic
lung injury.
铜绿假单胞菌引起急性院内肺炎以及
囊性纤维化患者的慢性肺部感染。其作用机制
对由此造成的肺损伤的责任尚不清楚。形成
诸如超氧化物和过氧化氢等氧化剂物种是相关的
有多种形式的肺损伤。在本项目最初的资助期内
程序中,我们获得了三个化合物活性分泌的证据。
铜绿假单胞菌通过氧化剂损伤肺上皮和内皮细胞
制作。在下一个资助期,我们将定义蜂窝
氧化还原循环的作用机制。这会产生超氧化物和
过氧化氢的产生。绿青素导致一系列有害物质
在体外和体内对细胞功能的影响。尽管如此,
关于细胞活动的数据有限。此外,
产生氧化剂的部位(S)、机理(S)和性质
花青素以及细胞靶标也鲜为人知。我们
假设绿色素介导的一系列复杂的效应发生
通过其诱导特定部位的氧化剂产生的能力
对细胞能量产生和氧化剂激活的干扰
敏感的信号通路。为了检验这一假设,有三个具体目标
都会实现的。目的1确定上皮细胞的致病机制(S)
紫外光照射下绿色素的细胞获取、细胞运输和代谢
在体外条件下。目标2是确定绿色素是如何消耗的。
通过确定绿青素对ATP和cAMP上皮细胞的影响
氧化磷酸化和糖酵解。这一目标还将解决以下问题
绿青素作用于氧化剂调节的信号通路,IL-8表达
将作为一个模范系统。前两个AIMS将使用体外培养
使用正常细胞和CF细胞的极化上皮细胞单层系统。
目标3将检查绿青素的体外作用程度
是在活体条件下观察到的。这项工作将集中在IL-8上
人呼吸道上皮细胞异种移植的释放和利用
SCID小鼠。这些研究将使用最先进的细胞技术
生物学和氧化化学定义新的和以前未曾探索过的
铜绿假单胞菌引起急性和/或慢性疾病的机制
肺损伤。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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BRADLEY E BRITIGAN其他文献
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{{ truncateString('BRADLEY E BRITIGAN', 18)}}的其他基金
Development of Gallium-Based Therapies for Pulmonary Mycobacterial Infections
肺部分枝杆菌感染的镓基疗法的开发
- 批准号:
9275424 - 财政年份:2014
- 资助金额:
$ 22.49万 - 项目类别:
Iron Acquisition by Mycobacterium tuberculosis Within Phagocytes
吞噬细胞内结核分枝杆菌对铁的获取
- 批准号:
7685175 - 财政年份:2009
- 资助金额:
$ 22.49万 - 项目类别:
Iron Acquisition by Mycobacterium tuberculosis Within Phagocytes
吞噬细胞内结核分枝杆菌对铁的获取
- 批准号:
8601148 - 财政年份:2009
- 资助金额:
$ 22.49万 - 项目类别:
Iron Acquisition by Mycobacterium tuberculosis Within Phagocytes
吞噬细胞内结核分枝杆菌对铁的获取
- 批准号:
8195964 - 财政年份:2009
- 资助金额:
$ 22.49万 - 项目类别:
Iron Acquisition by Mycobacterium tuberculosis Within Phagocytes
吞噬细胞内结核分枝杆菌对铁的获取
- 批准号:
7784541 - 财政年份:2009
- 资助金额:
$ 22.49万 - 项目类别:
Use of Gallium to Prevent Pseudomonas Biofilm Formation
使用镓防止假单胞菌生物膜形成
- 批准号:
6944895 - 财政年份:2004
- 资助金额:
$ 22.49万 - 项目类别:
Use of Gallium to Prevent Pseudomonas Biofilm Formation
使用镓防止假单胞菌生物膜形成
- 批准号:
6807809 - 财政年份:2004
- 资助金额:
$ 22.49万 - 项目类别:
PSEUDOMONAS PRODUCTS, OXYGEN RADICALS, AND LUNG INJURY
假单胞菌产物、氧自由基和肺损伤
- 批准号:
2607819 - 财政年份:1993
- 资助金额:
$ 22.49万 - 项目类别:
PSEUDOMONAS PRODUCTS, OXYGEN RADICALS, AND LUNG INJURY
假单胞菌产物、氧自由基和肺损伤
- 批准号:
2070249 - 财政年份:1993
- 资助金额:
$ 22.49万 - 项目类别:
PSEUDOMONAS PRODUCTS, OXYGEN RADICALS, AND LUNG INJURY
假单胞菌产物、氧自由基和肺损伤
- 批准号:
2004014 - 财政年份:1993
- 资助金额:
$ 22.49万 - 项目类别: