Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils
Autor: | Mark B. Hampton, Jürgen Bernhagen, Lisa Schindler, Nina Dickerhof, Leon Smyth |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Medicine (General) GSSG glutathione disulfide Neutrophils GSH reduced glutathione medicine.medical_treatment Clinical Biochemistry MPO myeloperoxidase Biochemistry Extracellular Traps MIF macrophage migration inhibitory factor chemistry.chemical_compound 0302 clinical medicine GSA glutathione sulfonamide GSSX glutathione present as a disulfide with other low molecular weight thiols PAF platelet-activating-factor Biology (General) Chemistry Superoxide Intramolecular Oxidoreductases Cytokine LPS lipopolysaccharide medicine.symptom Research Paper NETs neutrophil extracellular traps Hypochlorous acid LTB4 leukotriene B4 QH301-705.5 Phagocytosis Inflammation Microbiology 03 medical and health sciences R5-920 FITC fluorescein-5-isothiocyanate SOD superoxide dismutase PKC protein kinase C medicine OpZ opsonized zymosan Humans NE neutrophil elastase Macrophage Migration-Inhibitory Factors ARDS acute respiratory distress syndrome Organic Chemistry Zymosan PLA2 phospholipase A2 NETs Neutrophil extracellular traps Glutathione Neutrophil priming Hypochlorous Acid 030104 developmental biology Oxidative stress PMA phorbol 12-myristane 13-acetate DAMPs damage-associated molecular patterns NOX2 NADPH oxidase 2 Macrophage migration inhibitory factor BSA bovine serum albumin FCS fetal calf serum fMLP N-formyl-Met-Leu-Phe 4-IPP 4-iodo-6-phenylpyrimidine 030217 neurology & neurosurgery |
Zdroj: | Redox Biology Redox Biology, Vol 41, Iss, Pp 101946-(2021) |
ISSN: | 2213-2317 |
Popis: | 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. Graphical abstract Image 1 Highlights • MIF augments phagosomal HOCl production. • This results in increased oxidation of bacterial glutathione. • MIF increases superoxide production in response to soluble stimuli. • This results in increased NET formation. |
Databáze: | OpenAIRE |
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