Imperial College London
Alternate

ProfessorJonFriedland

Faculty of Medicine, Department of Infectious Disease

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 8521j.friedland Website

 
 
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Assistant

 

Ms Teyanna Gaeta +44 (0)20 3313 1943

 
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Location

 

8N21ACommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ong:2018:10.1038/s41598-018-29659-1,
author = {Ong, C and Fox, K and Ettorre, A and Elkington, P and Friedland, JS},
doi = {10.1038/s41598-018-29659-1},
journal = {Scientific Reports},
title = {Hypoxia increases neutrophil-driven matrix destruction after exposure to mycobacterium tuberculosis},
url = {http://dx.doi.org/10.1038/s41598-018-29659-1},
volume = {8},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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-1α, 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.
AU  - Ong,C
AU  - Fox,K
AU  - Ettorre,A
AU  - Elkington,P
AU  - Friedland,JS
DO  - 10.1038/s41598-018-29659-1
PY  - 2018///
SN  - 2045-2322
TI  - Hypoxia increases neutrophil-driven matrix destruction after exposure to mycobacterium tuberculosis
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-018-29659-1
UR  - http://hdl.handle.net/10044/1/62671
VL  - 8
ER  -
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