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

为了研究肺泡巨噬细胞（AM）在急性肺损伤（ALI）模型启动反应中的潜在作用，我们在第3天用cl2mda -脂质体（耗尽的启动AM）治疗WT小鼠，然后再用IT治疗。到第5天，与耗尽引物的AM组相比，未耗尽引物组表现出支气管肺泡灌洗（BAL）蛋白和BAL细胞的减少。肺组织学显示，非am -贫启动组在第5天损伤几乎完全消退；am缺失组间质增厚和肺实变持续存在。流式细胞术显示，在第0天，cl2mdp脂质体处理组超过90%的AMs被耗尽。与未耗尽AM组相比，缺失AM组在LPS作用后第1天BAL肿瘤坏死因子- α降低，第5天BAL IL-10升高。与启动的WT小鼠相比，il -10缺失小鼠在启动后没有加速肺损伤的消退。这些研究暗示am衍生的IL-10与LPS引发的ALI的加速分解有关。定义与启动相关的机制可以为潜在的ALI新疗法提供重要的见解。

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..