Inhibition of neutrophil elastase prevents neutrophil extracellular trap formation and rescues mice from endotoxic shock.

ABSTRACT: Neutrophil elastase (NE) is a serine protease stored in the azurophilic granules of neutrophils and released into the extracellular milieu during inflammatory response or formation of neutrophil extracellular traps (NETs). Neutrophils release NETs to entrap pathogens by externalizing their cellular contents in a DNA framework decorated with anti-microbials and proteases, including NE. Importantly, excess NETs in tissues are implicated in numerous pathologies, including sepsis, rheumatoid arthritis, vasculitis, and cancer. However, it remains unknown how to effectively prevent NET formation. Here, we show that NE plays a major role during NET formation and that inhibition of NE is a promising approach for decreasing NET-mediated tissue injury. NE promoted NET formation by human neutrophils.

SUBMITTER: Okeke EB 

PROVIDER: S-EPMC7075277 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature