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

Autor: Mark B. Hampton, Jürgen Bernhagen, Lisa Schindler, Nina Dickerhof, Leon Smyth
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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