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

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

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.

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.

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.