Blood:骨桥蛋白(OPN)介导输血相关的急性肺损伤的发生!

2019-05-13 MedSci MedSci原创

输血相关的急性肺损伤(TRALI)是输血相关死亡的主要原因之一,其特征是在输血后6小时内发生急性呼吸窘迫。目前尚无针对性的治疗方法。已有的炎症是TRALI的危险因素,而中性粒细胞(PMNs)被认为是主要的致病细胞。骨桥蛋白(OPN)是一种在炎症部位表达的多功能蛋白,介导肺部疾病、调节细胞迁移,并可作为PMN的趋化剂。Rick Kapur等人对OPN是否通过促进PMN招募到肺部从而促进TRALI的发

输血相关的急性肺损伤(TRALI)是输血相关死亡的主要原因之一,其特征是在输血后6小时内发生急性呼吸窘迫。目前尚无针对性的治疗方法。已有的炎症是TRALI的危险因素,而中性粒细胞(PMNs)被认为是主要的致病细胞。

骨桥蛋白(OPN)是一种在炎症部位表达的多功能蛋白,介导肺部疾病、调节细胞迁移,并可作为PMN的趋化剂。

Rick Kapur等人对OPN是否通过促进PMN招募到肺部从而促进TRALI的发生进行研究。研究人员通过已建立的小鼠TRALI模型,发现与野生型(WT)小鼠相反,OPN敲除(KO)小鼠对抗体介导的PMN依赖性TRALI诱导有耐受性。给OPN敲除小鼠注射纯化的OPN可恢复TRALI反应和肺部PMN积累。

此外,通过抗OPN抗体封闭野生型小鼠的OPN可预防TRALI诱导的发生。通过肺部免疫组化,研究人员发现OPN在TRALI小鼠的肺部特异性的被检测到。OPN介导的TRALI反应似乎是依赖于巨噬细胞(巨噬细胞可能是OPN的细胞来源)和OPN的聚合作用,但与OPN受体CD44、IL-6和其他PMN趋化因子(包括巨噬细胞炎性蛋白[MIP]-2)无关。

综上所述,本研究表明OPN通过定位于肺部和刺激肺部PMN招募对抗体介导的小鼠TRALI的诱导发生至关重要,提示抗OPN抗体疗法或可作为TRALI患者的潜在治疗策略。

原始出处:

Rick Kapur,et al. Osteopontin Mediates Murine Transfusion-Related Acute Lung Injury Via Stimulation of Pulmonary Neutrophil Accumulation.Blood 2019 :blood.2019000972; doi: https://doi.org/10.1182/blood.2019000972

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    2019-09-14 liuxiaona
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    2019-05-15 windight
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    2019-05-15 tastas

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