Neutrophil transfer of to lung epithelial cells dampens acute lung injury in mice.

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 (). Analysis of PMN-derived supernatants showed activation-dependent release of and subsequent transfer to alveolar epithelial cells during coculture in vitro or after ventilator-induced acute lung injury in mice. Genetic studies indicated that deficiency was associated with severe lung inflammation, whereas pulmonary overexpression of in mice resulted in protection during acute lung injury induced by mechanical ventilation or by infection with Studies of putative gene targets implicated repression of poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) in the -dependent attenuation of lung inflammation. Together, these findings suggest that intercellular transfer of from neutrophils to pulmonary epithelial cells may dampen acute lung injury through repression of PARP-1.