Zhang, Suisui, Huijun Dai, Lingyu Zhu, Fei Lin, Zhaokun Hu, Ren Jing, Weikang Zhang et al. “Microvesicles packaging IL-1β and TNF-α enhance lung inflammatory response to mechanical ventilation in part by induction of cofilin signaling.” International immunopharmacology 63 (2018): 74-83.

Zhang, Suisui, Huijun Dai, Lingyu Zhu, Fei Lin, Zhaokun Hu, Ren Jing, Weikang Zhang et al. "Microvesicles packaging IL-1β and TNF-α enhance lung inflammatory response to mechanical ventilation in part by induction of cofilin signaling." International immunopharmacology 63 (2018): 74-83.

Microvesicles shed from pulmonary cells are capable of transferring inflammatory cargo to recipient cells nearby or in distant to enhance inflammation. Some authors believe that cofilin controls actin dynamics and regulates vesicle mobilization. We therefore investigated the potential role and mechanism of microvesicles in ventilator-induced lung injury (VILI). Fifty male C57BL/6 mice were orotracheally intubated and either allowed to breathe spontaneously or they were mechanically ventilated with different tidal volumes (Vt) and ventilation times. Lung tissue injury was assessed in terms of lung histopathologicexamination, wet/dry weight ratios, and levels of total proteins and of cytokines. Microvesicle characteristics, sizes, contents and levels as well as cofilin were also measured. We found that lung inflammation increased significantly after ventilation with high Vt for 4 h; these conditions led to secretion of larger and more microvesicles into the alveoli than animals with/without ventilation at low Vt. Intratracheal instillation of microvesicles obtained from animals ventilated with low or high Vt triggered significant lung inflammation in naive mice, and these high-Vt microvesicles not only carried more IL-1β and TNF-α but also induced more severe lung inflammation compared to low-Vt microvesicles; And high-Vt microvesicles at 2 h carried more molecular cargo than that at 1 h or 4 h, which may involve the shift and amplification of inflammation. Furthermore, blocking the phosphorylation of cofilin can not only inhibit microvesicle formation in the lung, but also reduce lung injury. Collectively, our data suggest that microvesicles packaging IL-1β and TNF-α enhance lung inflammation in VILI.

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