Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity
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 comple...
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| Veröffentlicht in: | Blood 2011-01, Vol.117 (3), p.953-959 |
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| creator | Metzler, Kathleen D. Fuchs, Tobias A. Nauseef, William M. Reumaux, Dominique Roesler, Joachim Schulze, Ilka Wahn, Volker Papayannopoulos, Venizelos Zychlinsky, Arturo |
| description | 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. |
| doi_str_mv | 10.1182/blood-2010-06-290171 |
| format | Article |
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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.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2010-06-290171</identifier><identifier>PMID: 20974672</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Aniline Compounds - pharmacology ; Biological and medical sciences ; Blood Donors ; Blotting, Western ; Candida albicans - physiology ; Cells, Cultured ; Extracellular Space - drug effects ; Extracellular Space - immunology ; Extracellular Space - metabolism ; Genotype ; Hematologic and hematopoietic diseases ; Host-Pathogen Interactions ; Humans ; Immunity, Innate - immunology ; Medical sciences ; Microscopy, Fluorescence ; Mutation ; Neutrophils - immunology ; Neutrophils - metabolism ; Neutrophils - microbiology ; Peroxidase - antagonists & inhibitors ; Peroxidase - genetics ; Peroxidase - metabolism ; Phagocytes, Granulocytes, and Myelopoiesis ; Tetradecanoylphorbol Acetate - pharmacology</subject><ispartof>Blood, 2011-01, Vol.117 (3), p.953-959</ispartof><rights>2011 American Society of Hematology</rights><rights>2015 INIST-CNRS</rights><rights>2011 by The American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c558t-c801e9f984ad272a1ac3010b5d40b033e66a1db418175fcf8bb45d6e101753613</citedby><cites>FETCH-LOGICAL-c558t-c801e9f984ad272a1ac3010b5d40b033e66a1db418175fcf8bb45d6e101753613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23791221$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20974672$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Metzler, Kathleen D.</creatorcontrib><creatorcontrib>Fuchs, Tobias A.</creatorcontrib><creatorcontrib>Nauseef, William M.</creatorcontrib><creatorcontrib>Reumaux, Dominique</creatorcontrib><creatorcontrib>Roesler, Joachim</creatorcontrib><creatorcontrib>Schulze, Ilka</creatorcontrib><creatorcontrib>Wahn, Volker</creatorcontrib><creatorcontrib>Papayannopoulos, Venizelos</creatorcontrib><creatorcontrib>Zychlinsky, Arturo</creatorcontrib><title>Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity</title><title>Blood</title><addtitle>Blood</addtitle><description>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. 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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. 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| subjects | Aniline Compounds - pharmacology Biological and medical sciences Blood Donors Blotting, Western Candida albicans - physiology Cells, Cultured Extracellular Space - drug effects Extracellular Space - immunology Extracellular Space - metabolism Genotype Hematologic and hematopoietic diseases Host-Pathogen Interactions Humans Immunity, Innate - immunology Medical sciences Microscopy, Fluorescence Mutation Neutrophils - immunology Neutrophils - metabolism Neutrophils - microbiology Peroxidase - antagonists & inhibitors Peroxidase - genetics Peroxidase - metabolism Phagocytes, Granulocytes, and Myelopoiesis Tetradecanoylphorbol Acetate - pharmacology |
| title | Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity |
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