Research ArticleLUNG INJURY

Neutrophil transfer of miR-223 to lung epithelial cells dampens acute lung injury in mice

See allHide authors and affiliations

Science Translational Medicine  20 Sep 2017:
Vol. 9, Issue 408, eaah5360
DOI: 10.1126/scitranslmed.aah5360

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Starting an intercellular conversation

In a new study, Neudecker et al. show that transfer of microRNA-223 (miR-223) from neutrophils to lung alveoli helps to dampen lung inflammation and promotes the resolution of ventilator-induced lung injury in mice. The authors suggest that neutrophils secrete microRNAs in microvesicles that are then taken up by alveolar epithelial cells. They show that miR-223–deficient mice are prone to lung injury, whereas overexpression of miR-223 is protective.


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.

View Full Text