Myeloperoxidase is required for neutrophil extracellular trap formation
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Myeloperoxidase is required for neutrophil extracellular trap formation : implications for innate immunity. / Metzler, Kathleen D; Fuchs, Tobias A; Nauseef, William M; Reumaux, Dominique; Roesler, Joachim; Schulze, Ilka; Wahn, Volker; Papayannopoulos, Venizelos; Zychlinsky, Arturo.
In: BLOOD, Vol. 117, No. 3, 20.01.2011, p. 953-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Myeloperoxidase is required for neutrophil extracellular trap formation
T2 - implications for innate immunity
AU - Metzler, Kathleen D
AU - Fuchs, Tobias A
AU - Nauseef, William M
AU - Reumaux, Dominique
AU - Roesler, Joachim
AU - Schulze, Ilka
AU - Wahn, Volker
AU - Papayannopoulos, Venizelos
AU - Zychlinsky, Arturo
PY - 2011/1/20
Y1 - 2011/1/20
N2 - 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.
AB - 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.
KW - Aniline Compounds
KW - Blood Donors
KW - Blotting, Western
KW - Candida albicans
KW - Cells, Cultured
KW - Extracellular Space
KW - Genotype
KW - Host-Pathogen Interactions
KW - Humans
KW - Immunity, Innate
KW - Microscopy, Fluorescence
KW - Mutation
KW - Neutrophils
KW - Peroxidase
KW - Tetradecanoylphorbol Acetate
U2 - 10.1182/blood-2010-06-290171
DO - 10.1182/blood-2010-06-290171
M3 - SCORING: Journal article
C2 - 20974672
VL - 117
SP - 953
EP - 959
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 3
ER -