The Effects of Mechanical Ventilation on Neutrophil Extracellular Trap Formation

Mechanical ventilation can physically injure the lung and induce a proinflammatory state. Ventilator induced lung injury (VILI) is associated with neutrophil influx into the lung. Neutrophils can release DNA and granule proteins as cytotoxic neutrophil extracellular traps (NETs). This project aimed to determine if NETs were formed and contributed to injury in a two-hit LPS/VILI mouse model. We found that the combination of LPS and mechanical ventilation induced generation of NETs. High tidal volume mechanical ventilation increased release of HMGB1, an inducer of NETs, over low tidal volume control. The combination of LPS and high tidal volume was the greatest inducer of IL-1β, another potential inducer of NETs. Intratracheal DNase treatment reduced NETs and attenuated the loss of static compliance in the LPS/VILI model. NETosis represents a novel therapeutic target for VILI.MAS