Intercellular transfer of microRNAs can mediate communication between critical effector cells. We hypothesized that transfer of neutrophil-derived microRNAs to pulmonary epithelial cells could alter mucosal gene expression during acute lung injury. Pulmonary-epithelial microRNA profiling during coculture of alveolar epithelial cells with polymorphonuclear neutrophils (PMNs) revealed a selective increase in lung epithelial cell expression of microRNA-223 (miR-223). Analysis of PMN-derived supernatants showed activation-dependent release of miR-223 and subsequent transfer to alveolar epithelial cells during coculture in vitro or after ventilator-induced acute lung injury in mice. Genetic studies indicated that miR-223 deficiency was associated with severe lung inflammation, whereas pulmonary overexpression of miR-223 in mice resulted in protection during acute lung injury induced by mechanical ventilation or by infection with Staphylococcus aureus. Studies of putative miR-223 gene targets implicated repression of poly(adenosine diphosphate–ribose) polymerase–1 (PARP-1) in the miR-223–dependent attenuation of lung inflammation. Together, these findings suggest that intercellular transfer of miR-223 from neutrophils to pulmonary epithelial cells may dampen acute lung injury through repression of PARP-1.

microRNA的细胞间转移可以介导关键效应细胞之间的通讯。我们假设中性粒细胞来源的microRNA转移到肺上皮细胞可能会改变急性肺损伤期间黏膜基因表达。肺泡上皮细胞与多形核中性粒细胞（PMNs）共培养期间的肺上皮microRNA分析显示，microRNA-223（miR-223）肺上皮细胞表达选择性升高。对源自PMN的上清液的分析显示，在体外共培养期间或在呼吸机诱发的小鼠急性肺损伤后，miR-223的活化依赖性释放并随后转移至肺泡上皮细胞。遗传研究表明，miR-223缺乏与严重的肺部炎症有关，而miR-223在小鼠中的肺过度表达可在机械通气或金黄色葡萄球菌感染引起的急性肺损伤期间提供保护。推测的miR-223基因靶标的研究涉及在miR-223依赖性肺炎症减轻中抑制聚腺苷二磷酸核糖核糖聚合酶-1（PARP-1）。总之，这些发现表明，miR-223从嗜中性粒细胞向肺上皮细胞的细胞间转移可通过抑制PARP-1减轻急性肺损伤。