Inhaled bacterial mimetic increases PAD4-dependent NETosis in the lungs

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Title: Inhaled bacterial mimetic increases PAD4-dependent NETosis in the lungs Aims and Objectives: To establish an in vivo system to profile the impact of PAD4 inhibition in the mouse airway. Methods: Female C57bl/6NCrl mice were exposed to an aerosol of bacterial mimetic, LPS (1 mg/ml for 30 minutes). Markers and levels of NETosis and PAD activity were assessed in the BALF over time. Mice missing the functional enzyme were then used to determine the role of PAD4 in the system. Results: Over time, H3cit and citrullination activity were increased in the BALF of mice challenged with LPS compared to time-matched vehicle challenged controls. These increases were absent in mice missing functional PAD4. Conclusions: These data indicate that gram negative bacteria can trigger NETosis and PAD4 activity in the mouse airway. This model system could be useful in the search for a blocker of PAD4 activity and could lead to the development of a novel treatment of chronic respiratory diseases such as eg asthma and COPD.

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