Airway Nucleases and Surfactant Protein D in Neutrophil Extracellular Traps Clearance

Neutrophils release neutrophil extracellular traps (NETs) to trap and kill invading pathogens. However, NETs can damage host cells. A mechanism of NET clearance in the airways has not been established. We investigated whether NETs are cleaved by airway nucleases. Our study showed that nucleases are present in murine airways and that genomic DNA and NETs are cleaved in a magnesium/calcium- and calcium-dependent manner, respectively. We also found that these nucleases function optimally at specific pH ranges, such as near neutral pH and acidic pH. We also assessed the role of SP-D in NET clearance. We found that SP-D-deficient mice are defective in NET clearance compared to WT mice. SP-D supplemented to NET-alveolar macrophage (AM) cultures had fewer remaining NETs. Thus, we conclude that SP-D enhances the clearance of NETs by AMs. Overall, we conclude that nuclease digestion and SP-D are involved in the clearance of NETs in the airways.%%%%M.Sc.%%%%2018-06-13 00:00:00