| Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity. | |
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MedLine Citation:
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PMID: 20974672 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The granule enzyme myeloperoxidase (MPO) plays an important role in neutrophil antimicrobial responses. However, the severity of immunodeficiency in patients carrying mutations in MPO is variable. Serious microbial infections, especially with Candida species, have been observed in a subset of completely MPO-deficient patients. Here we show that neutrophils from donors who are completely deficient in MPO fail to form neutrophil extracellular traps (NETs), indicating that MPO is required for NET formation. In contrast, neutrophils from partially MPO-deficient donors make NETs, and pharmacological inhibition of MPO only delays and reduces NET formation. Extracellular products of MPO do not rescue NET formation, suggesting that MPO acts cell-autonomously. Finally, NET-dependent inhibition of Candida albicans growth is compromised in MPO-deficient neutrophils. The inability to form NETs may contribute in part to the host defense defects observed in completely MPO-deficient individuals. |
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Authors:
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Kathleen D Metzler; Tobias A Fuchs; William M Nauseef; Dominique Reumaux; Joachim Roesler; Ilka Schulze; Volker Wahn; Venizelos Papayannopoulos; Arturo Zychlinsky |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-10-25 |
Journal Detail:
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Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-21 Completed Date: 2011-04-14 Revised Date: 2012-01-20 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 953-9 Citation Subset: AIM; IM |
Affiliation:
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Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aniline Compounds
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pharmacology Blood Donors* Blotting, Western Candida albicans / physiology Cells, Cultured Extracellular Space / drug effects, immunology, metabolism* Genotype Host-Pathogen Interactions Humans Immunity, Innate / immunology Microscopy, Fluorescence Mutation Neutrophils / immunology, metabolism*, microbiology Peroxidase / antagonists & inhibitors, genetics, metabolism* Tetradecanoylphorbol Acetate / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI07958/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aniline Compounds; 16561-29-8/Tetradecanoylphorbol Acetate; 5351-17-7/4-aminobenzhydrazide; EC 1.11.1.7/Peroxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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