Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury
Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury
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DOI：
10.1172/jci38432
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发表时间：
2009-11-01
影响因子：
15.9
通讯作者：
Matthay, Michael A.
中科院分区：
文献类型：
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作者：
Looney, Mark R.;Nguyen, John X.;Matthay, Michael A.
输血相关急性肺损伤（TRA-LI）是美国输血相关死亡的主要原因。先前，我们建立了免疫介导的TRALI小鼠模型，其中具有同源抗原的小鼠用MHC I类mAb攻击。在这项研究中，当小鼠圈养在啮齿动物，特定的病原体无屏障室的挑战与MHC I单克隆抗体，有显着的保护，从TRALI相比，非屏障小鼠。用LPS致敏的小鼠通过mAb攻击恢复肺损伤。使用TLR 4缺陷骨髓嵌合体，打印表型仅限于WT造血细胞的动物，中性粒细胞或血小板的耗竭具有保护作用。中性粒细胞和血小板都被隔离在TRALI小鼠的肺中，血小板的保留依赖于中性粒细胞。有趣的是，用阿司匹林治疗可以防止肺损伤和死亡，但阻断P选择素或CD 11b/CD 18通路却不能。这些数据表明TRALI的两步机制：造血细胞的启动，随后是活化的中性粒细胞和血小板的血管沉积，然后介导严重的肺损伤。此外，我们的数据提供了一个解释的TRALI的发病率增加的患者与免疫启动条件，我们建议我们认为是一种新的治疗方法。
Transfusion-related acute lung injury (TRA-LI) is the leading cause of transfusion-associated mortality in the US. Previously, we established an immune-mediated TRALI mouse model, wherein mice with cognate antigen were challenged with MHC class I mAb. In this study, when mice housed in a rodent, specific pathogen-free barrier room were challenged with MHC I mAb, there was significant protection from TRALI compared with nonbarrier mice. Priming mice with LPS restored lung injury with mAb challenge. Using TLR4-deficient bone marrow chimeras, the printing phenotype was restricted to animals with WT hematopoietic cells, and depletion of either neutrophils or platelets was protective. Both neutrophils and platelets were sequestered in the lungs of mice with TRALI, and retention of platelets was neutrophil dependent. interestingly, treatment with aspirin prevented lung injury and mortality, but blocking the P selectin or CD11b/CD18 pathways did not. These data suggest a 2-step mechanism of TRALI: priming of hematopoietic cells, followed by vascular deposition of activated neutrophils and platelets that then mediate the severe lung injury. Furthermore, our data offer an explanation for the increased incidence of TRALI in patients with immune priming conditions, and we suggest what we believe to be a novel therapeutic approach.