The role of neutrophil extracellular traps in the pathogenesis of elastase-induced emphysema in mice

<bold>Aims and Objectives:</bold> Neutrophil extracellular traps (NETs) have been found to be involved in tissue damage and chronic inflammation. PAD4 (peptidylarginine deiminase 4) is a key enzyme that regulates the release of NETs. Formerly, we demonstrated that PAD4 deficiency Improves bleomycin-induced NETs and fibrosis in the lung of mouse. Although the presence of NETs has been found in the lungs of COPD patients, their role in emphysema formation remains undefined. Therefore, we examined the role of NETs in an elastase (ELS)-induced emphysema mouse model. <bold>Methods:</bold> We created an ELS-induced emphysema model using wild-type (Wt) (C57BL/6) and Padi4 gene knockout (padi4-/-, C57BL/6 background) (PAD4-KO) mice by intratracheal ELS instillation (3U/body). In the BALF, we evaluated the extent of NETs by immunostaining, and the number of total and differential cells. The extent of emphysema was analyzed by mean linear intercept (Lm) in the lungs, 14 days after the ELS instillation. <bold>Result:</bold> Intratracheal instillation of ELS to Wt mice showed formation of NETs in the BALF on day 1. In the BALF, the number of total cells (day1), neutrophils (day 1) were significantly reduced in PAD4-KO mice as compared to Wt mice. Moreover, the Lm of PAD4-KO mice was significantly lower than that of Wt (Wt vs PAD4-KO, 128.6±18.3 vs. 75.2±22.7 µm. p = 0.00173) 14 days after the ELS instillation. <bold>Conclusion:</bold> NETs may be involved in pulmonary inflammation and emphysema formation induced by ELS instillation.