权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Inter-cellular signal transduction by alveolar macrophages in acute lung injury

急性肺损伤中肺泡巨噬细胞的细胞间信号转导

基本信息

批准号：
07407045
负责人：
HASHIMOTO Satoru
金额：
$ 8.51万
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 (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

To examine the role of alveolar macrophages (AMs) in initial PMN recruitment after Gram-negative bacterial infection, we depleted AMs in rodent by aerosol inhalation of negatively charged large oligolamellar liposomes encapsulating clodronate disodium (Cl2MDP-liposomes). This method cleared over 95% of AMs from the lungs without causing lung damage or airspace neutrophilia. Depletion of AMS attenuated initial PMN recruitment and chemokine production in Pseudomonas aeruginosa pneumonia in rats. To further evaluate the role of AMs in acute and subacute Pseudomonas aeruginosa pneumonia in mice, AM-depleted mice and control mice were compared after intratracheally infected by P. aeruginosa. In addition to monitoring neutrophils recrutiment and chemokine releases, lung injury was evaluated soon after infection (8 h) and a later time (48 h). At 8 h, depletion of AMs reduced neutrophils recrutiment, chemokine release and lung injury. At 48 h, however, depletion of AMs decreased bacterial clearance and resulted in delayed movement of neutrophils from the site of inflammation with aggravated lung injury. In the setting of 50% lethal amount of bacteria instillation in control mice, the survival rate of AM-depleted mice showed low mortality within 24 h of infecton, but high mortality. at later time in contrast to non-AM-depleted mice. These results demonstrate that depletion of AMs has beneficial early effects but deleterious late effects on lung injury and survival in P. aeruginosa pneumonia.

为了研究肺泡巨噬细胞（AM）在革兰氏阴性细菌感染后初始PMN募集中的作用，我们通过雾化吸入包封氯膦酸二钠的带负电荷的大寡层脂质体（Cl 2 MDP-脂质体）来消耗啮齿动物中的AM。这种方法从肺部清除了超过95%的AM，而不会造成肺损伤或空气嗜酸性粒细胞。AMS消耗减弱了大鼠铜绿假单胞菌肺炎中初始PMN募集和趋化因子的产生。为了进一步评价AM在小鼠急性和亚急性铜绿假单胞菌肺炎中的作用，在铜绿假单胞菌肠道感染后比较AM去除的小鼠和对照小鼠。除了监测中性粒细胞的募集和趋化因子的释放，肺损伤后不久（8小时）和稍后的时间（48小时）进行了评价。在8小时，耗尽AM减少中性粒细胞的募集，趋化因子释放和肺损伤。然而，在48小时时，AM的消耗减少了细菌清除，并导致中性粒细胞从炎症部位的移动延迟，从而加剧了肺损伤。在对照组小鼠50%致死量细菌滴注的情况下，AM耗竭小鼠在感染后24 h内的存活率较低，但死亡率较高。与非AM耗尽的小鼠相比，在较晚的时间。这些结果表明，在铜绿假单胞菌肺炎中，AM的消耗对肺损伤和存活具有有益的早期效应，但具有有害的晚期效应。