Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils.

Völlger, Lena; Akong-Moore, Kathryn; Cox, Linda; Goldmann, Oliver; Wang, Yanming; Schäfer, Simon T; Naim, Hassan Y; Nizet, Victor; von Köckritz-Blickwede, Maren

dc.contributor.author	Völlger, Lena
dc.contributor.author	Akong-Moore, Kathryn
dc.contributor.author	Cox, Linda
dc.contributor.author	Goldmann, Oliver
dc.contributor.author	Wang, Yanming
dc.contributor.author	Schäfer, Simon T
dc.contributor.author	Naim, Hassan Y
dc.contributor.author	Nizet, Victor
dc.contributor.author	von Köckritz-Blickwede, Maren
dc.date.accessioned	2016-05-25T08:54:40Z	en
dc.date.available	2016-05-25T08:54:40Z	en
dc.date.issued	2016-07	en
dc.identifier.citation	Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils. 2016, 36 (3): Biosci. Rep.	en
dc.identifier.issn	1573-4935	en
dc.identifier.pmid	27129288	en
dc.identifier.doi	10.1042/BSR20160031	en
dc.identifier.uri	http://hdl.handle.net/10033/610674	en
dc.description.abstract	Neutrophil extracellular trap (NET) formation is a significant innate immune defense mechanism against microbial infection that complements other neutrophil functions including phagocytosis and degranulation of antimicrobial peptides. NETs are decondensed chromatin structures in which antimicrobial components (histones, antimicrobial peptides and proteases) are deployed and mediate immobilization of microbes. Here we describe an effect of iron chelation on the phenotype of NET formation. Iron-chelating agent desferrioxamine (DFO) showed a modest but significant induction of NETs by freshly isolated human neutrophils as visualized and quantified by immunocytochemistry against histone-DNA complexes. Further analyses revealed that NET induction by iron chelation required NADPH-dependent production of reactive oxygen species (ROS) as well as protease and peptidyl-arginine-deiminase 4 (PAD4) activities, three key mechanistic pathways previously linked to NET formation. Our results demonstrate that iron chelation by DFO contributes to the formation of NETs and suggest a target for pharmacological manipulation of NET activity.
dc.language.iso	en	en
dc.title	Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils.	en
dc.type	Article	en
dc.contributor.department	Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.	en
dc.identifier.journal	Bioscience reports	en
refterms.dateFOA	2018-06-12T23:41:57Z
html.description.abstract	Neutrophil extracellular trap (NET) formation is a significant innate immune defense mechanism against microbial infection that complements other neutrophil functions including phagocytosis and degranulation of antimicrobial peptides. NETs are decondensed chromatin structures in which antimicrobial components (histones, antimicrobial peptides and proteases) are deployed and mediate immobilization of microbes. Here we describe an effect of iron chelation on the phenotype of NET formation. Iron-chelating agent desferrioxamine (DFO) showed a modest but significant induction of NETs by freshly isolated human neutrophils as visualized and quantified by immunocytochemistry against histone-DNA complexes. Further analyses revealed that NET induction by iron chelation required NADPH-dependent production of reactive oxygen species (ROS) as well as protease and peptidyl-arginine-deiminase 4 (PAD4) activities, three key mechanistic pathways previously linked to NET formation. Our results demonstrate that iron chelation by DFO contributes to the formation of NETs and suggest a target for pharmacological manipulation of NET activity.