Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases.

ABSTRACT: Papillon-Lefèvre syndrome (PLS) is characterized by nonfunctional neutrophil serine proteases (NSPs) and fulminant periodontal inflammation of unknown cause. Here we investigated neutrophil extracellular trap (NET)-associated aggregation and cytokine/chemokine-release/degradation by normal and NSP-deficient human and mouse granulocytes. Stimulated with solid or soluble NET inducers, normal neutrophils formed aggregates and both released and degraded cytokines/chemokines. With increasing cell density, proteolytic degradation outweighed release. Maximum output of cytokines/chemokines occurred mostly at densities between 2 × 10⁷ and 4 × 10⁷ neutrophils/cm³. Assessment of neutrophil density in vivo showed that these concentrations are surpassed during inflammat

SUBMITTER: Hahn J 

PROVIDER: S-EPMC6355082 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature