Neutrophils and their Fcγ receptors are essential in a mouse model of transfusion-related acute lung injury
Neutrophils and their Fcγ receptors are essential in a mouse model of transfusion-related acute lung injury
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DOI：
10.1172/jci27238
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发表时间：
2006-06-01
影响因子：
15.9
通讯作者：
Matthay, Michael A.
中科院分区：
文献类型：
--
作者：
Looney, Mark R.;Su, Xiao;Matthay, Michael A.
输血相关急性肺损伤（TRALI）是输血相关死亡的最常见原因。为了探索TRALI的发病机制，我们开发了一种体内小鼠模型，该模型基于将MHC I类（MHC I）mAb（H2 K（d））被动输注给具有同源抗原的小鼠。给BALB/c小鼠输注MHC I mAb产生急性肺损伤，肺水过多，肺血管和肺上皮对蛋白质的通透性增加，肺泡液体清除率降低。在Ab给药后2小时的时间点有50%的死亡率。肺组织学和免疫组织化学显示肺微血管中显著的中性粒细胞隔离，其伴随急性外周血中性粒细胞减少症发生，均在mAb给药后2小时内发生。通过注射抗粒细胞mAb Gr-1消耗中性粒细胞保护小鼠免受MHC I mAb攻击后的肺损伤。FcR γ（-/-）小鼠对MHC I mAb诱导的肺损伤具有抗性，而将野生型嗜中性粒细胞过继转移到FcR γ（-/-）动物中恢复了MHC I ntAb攻击后的肺损伤。总之，在使用MHC I mAb的TRALI临床相关体内小鼠模型中，肺损伤机制依赖于中性粒细胞及其Fc γ受体。
Transfusion-related acute lung injury (TRALI) is the most common cause of transfusion-related mortality. To explore the pathogenesis of TRALI, we developed an in vivo mouse model based on the passive transfusion of an MHC class I (MHC I) mAb (H2K(d)) to mice with the cognate antigen. Transfusion of the MHC I mAb to BALB/c mice produced acute lung injury with increased excess lung water, increased lung vascular and lung epithelial permeability to protein, and decreased alveolar fluid clearance. There was 50% mortality at a 2-hour time point after Ab administration. Pulmonary histology and immunohistochemistry revealed prominent neutrophil sequestration in the lung microvasculature that occurred concomitantly with acute peripheral blood neutropenia, all within 2 hours of administration of the mAb. Depletion of neutrophils by injection of anti-granulocyte mAb Gr-1 protected mice from lung injury following MHC I mAb challenge. FcR gamma(-/-) mice were resistant to MHC I mAb-induced lung injury, while adoptive transfer of wild-type neutrophils into the FcR gamma(-/-) animals restored lung injury following MHC I ntAb challenge. In conclusion, in a clinically relevant in vivo mouse model of TRALI using an MHC I mAb, the mechanism of lung injury was dependent on neutrophils and their Fc gamma receptors.