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The pathophysiology of intratracheal LPS or BLM lung injury mice model after LPS-priming

LPS启动后气管内LPS或BLM肺损伤小鼠模型的病理生理学

基本信息

批准号：
22590854
负责人：
TSUSHIMA Kenji
金额：
$ 2.91万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

To examine potential roles for alveolar macrophages (AM) in the priming response in model of acute lung injury (ALI), primed WT mice were treated with Cl2MDP-liposome (depleted primed AM) on day -3 followed by IT． By day 5, the non-depleted primed group exhibited reduced bronchoalveolar lavage (BAL) protein and BAL cells compared to depleted primed AM group. Lung histology revealed nearly complete resolution of injury on day 5 in non-AM-depleted primed group; interstitial thickening and lung consolidation persisted in the AM-depleted primed group. Flow cytometry revealed thatat day 0 over 90% of AMs were depleted in the Cl2MDP-liposome treated group. BAL tumor necrosis factor-alpha was lower on day 1 and was higher on day 5 in depleted primed AM group compared to non-depleted primed AM group while BAL IL-10 was higher in non-depleted primed AM group on day 1 after LPS. In contrast to primed WT mice, IL-10-null mice did not exhibit accelerated resolution of lung injury with priming. These studies implicate AM-derived IL-10 in the accelerated resolution of ALI produced by LPS priming. Definition of mechanisms related to priming could provide important insights into potential new therapies for ALI..

为探讨肺泡巨噬细胞(AM)在急性肺损伤(ALI)模型预激反应中的作用，用Cl2MDP-脂质体(去势预激AM)处理WT小鼠，第3天后IT，第5天非耗竭预激组小鼠的BAL蛋白和BAL细胞数较耗竭预激AM组减少。肺组织学显示非AM耗竭预充组第5天损伤几乎完全消失；AM耗竭预充组间质增厚和肺实变持续存在。流式细胞仪检测显示，Cl2MDP-脂质体处理组在0d时90%以上的AM被耗尽。耗竭预激AM组与非耗竭预激AM组相比，BAL肿瘤坏死因子-α在第1天降低，第5天升高，而BAL IL-10在第1天高于非耗竭预激AM组。与预充WT小鼠相比，IL-10缺失的小鼠未表现出预充可加速肺损伤的消退。这些研究表明，AM来源的IL-10参与了脂多糖诱导的ALI的加速分解。与启动相关的机制的定义可以为ALI潜在的新疗法提供重要的见解。