Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-018-29659-1
Title: Hypoxia increases neutrophil-driven matrix destruction after exposure to Mycobacterium tuberculosis
Authors: Ong, C.W.M 
Fox, K
Ettorre, A
Elkington, P.T
Friedland, J.S
Keywords: apoptosome
gelatinase B
hypoxia inducible factor 1alpha
neutrophil collagenase
pancreatic elastase
cell line
human
hypoxia
immunology
lung
monocyte
Mycobacterium tuberculosis
neutrophil
signal transduction
tuberculosis
upregulation
Apoptosomes
Cell Line
Humans
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit
Lung
Matrix Metalloproteinase 8
Matrix Metalloproteinase 9
Monocytes
Mycobacterium tuberculosis
Neutrophils
Pancreatic Elastase
Signal Transduction
Tuberculosis
Up-Regulation
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Ong, C.W.M, Fox, K, Ettorre, A, Elkington, P.T, Friedland, J.S (2018). Hypoxia increases neutrophil-driven matrix destruction after exposure to Mycobacterium tuberculosis. Scientific Reports 8 (1) : 11475. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-018-29659-1
Rights: Attribution 4.0 International
Abstract: The importance of neutrophils in the pathology of tuberculosis (TB) has been recently established. We demonstrated that TB lesions in man are hypoxic, but how neutrophils in hypoxia influence lung tissue damage is unknown. We investigated the effect of hypoxia on neutrophil-derived enzymes and tissue destruction in TB. Human neutrophils were stimulated with M. tuberculosis (M.tb) or conditioned media from M.tb-infected monocytes (CoMTB). Neutrophil matrix metalloproteinase-8/-9 and elastase secretion were analysed by luminex array and gelatin zymography, gene expression by qPCR and cell viability by flow cytometry. Matrix destruction was investigated by confocal microscopy and functional assays and neutrophil extracellular traps (NETs) by fluorescence assay. In hypoxia, neutrophil MMP-8 secretion and gene expression were up-regulated by CoMTB. MMP-9 activity and neutrophil elastase (NE) secretion were also increased in hypoxia. Hypoxia inhibited NET formation and both neutrophil apoptosis and necrosis after direct stimulation by M.tb. Hypoxia increased TB-dependent neutrophil-mediated matrix destruction of Type I collagen, gelatin and elastin, the main structural proteins of the human lung. Dimethyloxalylglycin (DMOG), which stabilizes hypoxia-inducible factor-1?, increased neutrophil MMP-8 and -9 secretion. Hypoxia in our cellular model of TB up-regulated pathways that increase neutrophil secretion of MMPs that are implicated in matrix destruction. © 2018, The Author(s).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/178399
ISSN: 2045-2322
DOI: 10.1038/s41598-018-29659-1
Rights: Attribution 4.0 International
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