Mechanism of cell damage and repair in acute lung injury

急性肺损伤的细胞损伤与修复机制

基本信息

批准号：
16390457
负责人：
HASHIMOTO Satoru
金额：
$ 8.53万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390457/
关键词：
Acute lung injury HMGB1 Microsampling Ventilator induced lung iniury Fas FasL アポトーシスラミニン ATP モエシン ARDS 急性肺障害

项目摘要

The first study was performed to examine the putative role of high-mobility group box (HMGB) protein in the pathogenesis of acute lung injury. Observations were made 1) in 21 septic patients with acute lung injury and 15 patients with normal lung function, and 2) in a mouse model, 24 h after intratracheal instillation of lipopolysaccharide. The concentrations of HMGB 1 were increased in plasma and lung epithelial lining fluid of patients with acute lung injury and mice instilled with lipopolysaccharide. Lipopolysaccharide-induced acute lung injury was mitigated by anti-HMGB1 antibody. Although this protein was not detected in the plasma of control humans or mice, the concentrations of HMGB 1 in lung epithelial lining fluid or in bronchoalveolar lavage fluid were unexpectedly high. The nuclear expression of HMGB 1 was apparent in epithelial cells surrounding terminal bronchioles in normal mice, while its nuclear and cytoplasmic expression was observed in alveolar macrophages in lipopoly … More saccharide-instilled mice. Lung instillation of HMGB2 did not cause as much inflammation as HMGB 1. Extracellular HMGB 1 may play a key role in the pathogenesis of clinical and experimental acute lung injury. However, its expression in normal airways is noteworthy, and suggests that it also plays a physiologic role in the lung. And the second study was about Fas/FasL system. Alveolar epithelial cell death plays a crucial role in the progression of acute lung injury. We have demonstrated up-regulation of Fas expression on alveolar epithelial cells, and soluble Fas ligand secretion from inflammatory cells upon acute lung injury. Here we show that the lipopolysaccharide-stimulated human monocyte cell line THP-1 releases Fas ligand, and that conditioned medium from lipopolysaccharide-stimulated THP-1 cells induces apoptosis of the human pulmonary adenocarcinoma cell line A549. Activation of caspase-3 and -8 is associated with the apoptosis. Gene targeting on Fas in A549 cells by specific small interfering RNA impairs apoptosis induced by conditioned medium from activated THP-1, while that on Fas ligand in THP-1 cells impairs the apoptosis-inducing activity of the conditioned medium produced by lipopolysaccharide-stimulated cells. These results suggest that Fas ligand released by monocytes causes alveolar epithelial cell death through a Fas-dependent apoptotic mechanism in the development of acute lung injury. Less

在21例肺部损伤患者中进行了第一项研究，以高运动组盒（HMGB）蛋白在急性肺的发病机理中的推定作用。小鼠模型，急性肺和小鼠的静脉内液体含量为24小时。流体或支气管肺泡灌洗液中的核表达是在正常遗迹中明显的HMGB2的滴注不如HMGB 1。细胞外HMGB 1可能在临床轴心急性肺损伤的发病机理中起着AKEY的作用。在进展的肺部损伤中，我们在肺泡上皮上表现出FAS的上调，并在急性肺部损伤中向炎症细胞提供了FAS。 1释放FAS配体，从脂多糖刺激的THP -1细胞中诱导人肺rcinoma rcinoma rcinoma cyl a549的凋亡。细胞会损害损害脂多糖刺激的细胞产生的分离培养基的凋亡型的凋亡，这些结果表明，单核细胞释放的FAS配体肺泡细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞池细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞</s> </s> </s> </s>

项目成果

期刊论文数量（30）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

High mobility group protein (HMGB1) as a possible mediator of acute exacerbation in idiopathic pulmonary fibrosis

高迁移率族蛋白（HMGB1）作为特发性肺纤维化急性加重的可能介质

DOI：
发表时间：
2005
期刊：
影响因子：
0
作者：
Ebina;M.;Kimura;Y.;Shibata;N.;Konishi;K.;Ishizaka;A.;Hashimoto;S.;MaruyamaI;Nukiwa;T
通讯作者：
T

Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid

DOI：
10.1111/j.1440-1843.2007.01208.x
发表时间：
2008-03-01
期刊：
RESPIROLOGY
影响因子：
6.9
作者：
Kikuchi, Eiki;Yamazaki, Koichi;Nishimura, Masaharu
通讯作者：
Nishimura, Masaharu

Measurement of neutrophil elastase activity in ARDS patients treated with neutrophil elastase inhibitor

中性粒细胞弹性蛋白酶抑制剂治疗的 ARDS 患者中性粒细胞弹性蛋白酶活性的测定

DOI：
发表时间：
2005
期刊：
影响因子：
0
作者：
Hashimoto;S.;Okayama;Y.;Shime;N.;Amaya;F.;Ishizaka;A
通讯作者：
A

Endothelin-1 levels of serum and epithelial lining fluid in ALI/ARDS

ALI/ARDS 患者血清和上皮衬里液的内皮素-1 水平

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Nakano;Y.;S.;Tasaka;Hashimoto;S.;Ogawa;Y.;Kurihara;A.;Saito;F.;Yamada;W.;Shimizu;M.;Koh;H.;Nakamura;M.;Hasegawa;N.;Fujishima;S.;Ishizaka;A
通讯作者：
A

Effects of controlled perioperative antimicrobial prophylaxis on infectious outcomes in pediatric cardiac surgery