Neutrophil Dysfunction in the Airways of Children with Acute Respiratory Failure Due to Lower Respiratory Tract Viral and Bacterial Coinfections
Neutrophil Dysfunction in the Airways of Children with Acute Respiratory Failure Due to Lower Respiratory Tract Viral and Bacterial Coinfections
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DOI：
10.1038/s41598-019-39726-w
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发表时间：
2019-02-27
影响因子：
4.6
通讯作者：
Tirouvanziam, Rabindra
中科院分区：
文献类型：
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作者：
Grunwell, Jocelyn R.;Giacalone, Vincent D.;Tirouvanziam, Rabindra
中性粒细胞被招募到急性呼吸窘迫综合征（ARDS）患者的气道中，在那里它们获得激活的促生存表型，并增强呼吸爆发，被认为有助于ARDS病理生理。我们的体外模型使血液中性粒细胞经上皮迁移到患者无细胞的气管抽吸液中，以重现在体内观察到的原发性气道中性粒细胞表型。下呼吸道病毒感染合并细菌感染的儿童的中性粒细胞通过我们的模型转移到气道液中，中性粒细胞激活标记物水平升高，但与没有细菌合并感染的儿童相比，矛盾的是，中性粒细胞表现出无法杀死细菌和有缺陷的呼吸爆发。与无细菌合并感染的儿童相比，合并细菌合并感染的儿童气道液中中性粒细胞弹性酶活性和髓过氧化物酶水平较高。从合并细菌感染的儿童身上转移到吸出液中的中性粒细胞与从没有合并细菌感染的儿童身上转移到吸出液中的中性粒细胞相比，显示出呼吸爆发和对流感嗜血杆菌和金黄色葡萄球菌的杀伤活性降低。使用一种新的转运模型概括了这种体外病理表型，否则在患者中是不可能的，为未来的机制和治疗研究开辟了道路。
Neutrophils are recruited to the airways of patients with acute respiratory distress syndrome ( ARDS) where they acquire an activated pro-survival phenotype with an enhanced respiratory burst thought to contribute to ARDS pathophysiology. Our in vitro model enables blood neutrophil transepithelial migration into cell-free tracheal aspirate fluid from patients to recapitulate the primary airway neutrophil phenotype observed in vivo. Neutrophils transmigrated through our model toward airway fluid from children with lower respiratory viral infections coinfected with bacteria had elevated levels of neutrophil activation markers but paradoxically exhibited an inability to kill bacteria and a defective respiratory burst compared with children without bacterial coinfection. The airway fluid from children with bacterial coinfections had higher levels of neutrophil elastase activity, as well as myeloperoxidase levels compared to children without bacterial coinfection. Neutrophils transmigrated into the aspirate fluid from children with bacterial coinfection showed decreased respiratory burst and killing activity against H. influenzae and S. aureus compared to those transmigrated into the aspirate fluid from children without bacterial coinfection. Use of a novel transmigration model recapitulates this pathological phenotype in vitro that would otherwise be impossible in a patient, opening avenues for future mechanistic and therapeutic research.