Treatment with DNases rescues hidden neutrophil elastase from aggregated NETs

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Malgorzata J. Podolska¹  Aparna Mahajan¹  Jonas Hahn¹  Jasmin Knopf¹  Christian Maueröder¹  Lenka Petru¹  Marc Ullmann¹  Georg Schett¹  Moritz Leppkes⁵  Martin Herrmann¹  Luis E. Muñoz¹  Christine Schauer¹ 

[1] Department of Internal Medicine 3—Rheumatology and Immunology;Cell Clearance in Health and Disease Lab, VIB Center for Inflammation Research;Department of Biomedical Molecular Biology, Ghent University;Department of Rheumatology, First Faculty of Medicine, Charles University-Institute of Rheumatology;Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine 1—Gastroenterology

关键词: aggregated NETs;    DNase 1;    NETs;    neutrophil elastase;    neutrophils;   

DOI  :  10.1002/JLB.3AB0918-370R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY