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Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils

BACKGROUND: Macrophage migration inhibitory factor (MIF) is an important immuno-regulatory cytokine and is elevated in inflammatory conditions. Neutrophils are the first immune cells to migrate to sites of infection and inflammation, where they generate, among other mediators, the potent oxidant hyp...

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Autores principales: Schindler, Lisa, Smyth, Leon C.D., Bernhagen, Jürgen, Hampton, Mark B., Dickerhof, Nina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047225/
https://www.ncbi.nlm.nih.gov/pubmed/33823474
http://dx.doi.org/10.1016/j.redox.2021.101946
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author Schindler, Lisa
Smyth, Leon C.D.
Bernhagen, Jürgen
Hampton, Mark B.
Dickerhof, Nina
author_facet Schindler, Lisa
Smyth, Leon C.D.
Bernhagen, Jürgen
Hampton, Mark B.
Dickerhof, Nina
author_sort Schindler, Lisa
collection PubMed
description BACKGROUND: Macrophage migration inhibitory factor (MIF) is an important immuno-regulatory cytokine and is elevated in inflammatory conditions. Neutrophils are the first immune cells to migrate to sites of infection and inflammation, where they generate, among other mediators, the potent oxidant hypochlorous acid (HOCl). Here, we investigated the impact of MIF on HOCl production in neutrophils in response to phagocytic stimuli. METHODS: Production of HOCl during phagocytosis of zymosan was determined using the specific fluorescent probe R19-S in combination with flow cytometry and live cell microscopy. The rate of phagocytosis was monitored using fluorescently-labeled zymosan. Alternatively, HOCl production was assessed during phagocytosis of Pseudomonas aeruginosa by measuring the oxidation of bacterial glutathione to the HOCl-specific product glutathione sulfonamide. Formation of neutrophil extracellular traps (NETs), an oxidant-dependent process, was quantified using a SYTOX Green plate assay. RESULTS: Exposure of human neutrophils to MIF doubled the proportion of neutrophils producing HOCl during early stages of zymosan phagocytosis, and the concentration of HOCl produced was greater. During phagocytosis of P. aeruginosa, a greater fraction of bacterial glutathione was oxidized to glutathione sulfonamide in MIF-treated compared to control neutrophils. The ability of MIF to increase neutrophil HOCl production was independent of the rate of phagocytosis and could be blocked by the MIF inhibitor 4-IPP. Neutrophils pre-treated with MIF produced more NETs than control cells in response to PMA. CONCLUSION: Our results suggest a role for MIF in potentiating HOCl production in neutrophils in response to phagocytic stimuli. We propose that this newly discovered activity of MIF contributes to its role in mediating the inflammatory response and enhances host defence.
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spelling pubmed-80472252021-04-16 Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils Schindler, Lisa Smyth, Leon C.D. Bernhagen, Jürgen Hampton, Mark B. Dickerhof, Nina Redox Biol Research Paper BACKGROUND: Macrophage migration inhibitory factor (MIF) is an important immuno-regulatory cytokine and is elevated in inflammatory conditions. Neutrophils are the first immune cells to migrate to sites of infection and inflammation, where they generate, among other mediators, the potent oxidant hypochlorous acid (HOCl). Here, we investigated the impact of MIF on HOCl production in neutrophils in response to phagocytic stimuli. METHODS: Production of HOCl during phagocytosis of zymosan was determined using the specific fluorescent probe R19-S in combination with flow cytometry and live cell microscopy. The rate of phagocytosis was monitored using fluorescently-labeled zymosan. Alternatively, HOCl production was assessed during phagocytosis of Pseudomonas aeruginosa by measuring the oxidation of bacterial glutathione to the HOCl-specific product glutathione sulfonamide. Formation of neutrophil extracellular traps (NETs), an oxidant-dependent process, was quantified using a SYTOX Green plate assay. RESULTS: Exposure of human neutrophils to MIF doubled the proportion of neutrophils producing HOCl during early stages of zymosan phagocytosis, and the concentration of HOCl produced was greater. During phagocytosis of P. aeruginosa, a greater fraction of bacterial glutathione was oxidized to glutathione sulfonamide in MIF-treated compared to control neutrophils. The ability of MIF to increase neutrophil HOCl production was independent of the rate of phagocytosis and could be blocked by the MIF inhibitor 4-IPP. Neutrophils pre-treated with MIF produced more NETs than control cells in response to PMA. CONCLUSION: Our results suggest a role for MIF in potentiating HOCl production in neutrophils in response to phagocytic stimuli. We propose that this newly discovered activity of MIF contributes to its role in mediating the inflammatory response and enhances host defence. Elsevier 2021-03-30 /pmc/articles/PMC8047225/ /pubmed/33823474 http://dx.doi.org/10.1016/j.redox.2021.101946 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Schindler, Lisa
Smyth, Leon C.D.
Bernhagen, Jürgen
Hampton, Mark B.
Dickerhof, Nina
Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils
title Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils
title_full Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils
title_fullStr Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils
title_full_unstemmed Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils
title_short Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils
title_sort macrophage migration inhibitory factor (mif) enhances hypochlorous acid production in phagocytic neutrophils
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047225/
https://www.ncbi.nlm.nih.gov/pubmed/33823474
http://dx.doi.org/10.1016/j.redox.2021.101946
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