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Treatment with DNases rescues hidden neutrophil elastase from aggregated NETs
Author(s) -
Podolska Malgorzata J.,
Mahajan Aparna,
Hahn Jonas,
Knopf Jasmin,
Maueröder Christian,
Petru Lenka,
Ullmann Marc,
Schett Georg,
Leppkes Moritz,
Herrmann Martin,
Muñoz Luis E.,
Schauer Christine
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.3ab0918-370r
Subject(s) - neutrophil extracellular traps , neutrophil elastase , biology , serine protease , inflammation , elastase , chromatin , proteases , extracellular , microbiology and biotechnology , immunology , enzyme , protease , gene , biochemistry
Abstract The release of neutrophil extracellular traps (NETs) is one of the weapons neutrophils have in their armory. NETs consist of extracellular chromatin fibers decorated with a plethora of cytoplasmic and granular proteins, such as the antimicrobial serine protease neutrophil elastase (NE). Because the first description of NETs as beneficial to the host, reports on their double‐faced role in health and disease have considerably increased recently. On one hand, NETs reportedly trap and kill bacteria and also participate in the resolution of the acute inflammation associated with infection and with tissue damage. On the other hand, numerous negative aspects of NETs contribute to the etiopathogenesis of autoimmune disorders. Employing soluble and solid fluorescent substrates, we demonstrate the interaction of NE with aggregated NETs (aggNETs), the limitation of its enzymatic activity and the containment of the enzyme from surrounding tissues. These events prevent the spread of inflammation and tissue damage. The detection of DNase 1‐dependent elevation of NE activity attests the continuous presence of patrolling neutrophils forming NETs and aggNETs even under conditions physiologic conditions.