Roles of lung-recruited monocytes and pulmonary Vascular Endothelial Growth Factor (VEGF) in resolving Ventilator-Induced Lung Injury (VILI)

Abstract

Monocytes and vascular endothelial growth factor (VEGF) have profound effects on tissue injury and repair. In ventilator-induced lung injury (VILI), monocytes, the majority of which are Ly6C+high, and VEGF are known to initiate lung injury. However, their roles in post-VILI lung repair remain unclear. In this study, we used a two-hit mouse model of VILI to identify the phenotypes of monocytes recruited to the lungs during the resolution of VILI and investigated the contributions of monocytes and VEGF to lung repair. We found that the lung-recruited monocytes were predominantly Ly6C+low from day 1 after the insult. Meanwhile, contrary to inflammatory cytokines, pulmonary VEGF decreased upon VILI but subsequently increased significantly on days 7 and 14 after the injury. There was a strong positive correlation between VEGF expression and proliferation of alveolar epithelial cells in lung sections. The expression pattern of VEGF mRNA in lung-recruited monocytes was similar to that of pulmonary VEGF proteins, and the depletion of monocytes significantly suppressed the increase of pulmonary VEGF proteins on days 7 and 14 after VILI. In conclusion, during recovery from VILI, the temporal expression patterns of pulmonary growth factors are different from those of inflammatory cytokines, and the restoration of pulmonary VEGF by monocytes, which are mostly Ly6C+low, is associated with pulmonary epithelial proliferation. Lung-recruited monocytes and pulmonary VEGF may play crucial roles in post-VILI lung repair.