M1 Macrophage Activated by Notch Signal Pathway Contributed to Ventilator-Induced Lung Injury in Chronic Obstructive Pulmonary Disease Model

Abstract Background Ventilator-induced lung injury (VILI) in chronic obstructive pulmonary disease (COPD) is still a problem. We intended to explore the role of macrophage polarity in VILI and the underlying mechanism. Materials and methods COPD model was created by cigarette smoke and ventilated. Macrophages were isolated, and the wet/dry (W/D) ratio was determined after modeling, and proteins in bronchoalveolar lavage fluid (BALF) were assessed by bicinchoninic acid assay. Histopathology was observed by Hematoxylin-Eosin staining. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured by enzyme-linked immunosorbent assay. Macrophage polarity was assessed by flow cytometry. Protein levels were measured by Western blot and mRNA by quantitative real-time polymerase chain reaction. Results Pathology statement was worsened, and the W/D ratio, protein level in BALF, TNF-α level, and IL-6 levels were elevated in cigarette smoke–induced COPD model. Notch-1 intracellular domain, hairy and enhancer of split (Hes) 1, Hes5, hairy/enhancer-of-split related with YRPW motif protein 1, CD86, TNF-α, and inducible nitric oxide synthases expressions were raised, whereas CD206, IL-4, and IL-10 expressions were decreased in macrophages after ventilation, shifting macrophage polarity to M1 phenotype. After the inhibition of Notch signaling, pathology statement was improved, and the W/D ratio, protein level in BALF, TNF-α, IL-6, Notch-1 intracellular domain, Hes1, Hes5, hairy/enhancer-of-split related with YRPW motif protein 1, CD86, TNF-α, and inducible nitric oxide synthases expressions were decreased while CD206, IL-4, and IL-10 expressions were elevated after ventilation, shifting macrophage polarity to M2 phenotype partially. Conclusions Mechanical ventilation in cigarette-induced COPD could activate the Notch signal pathway and further shift the polarity of macrophage toward M1 phenotype, leading to VILI in cigarette-induced COPD.