Imperial College London
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Emeritus ProfessorEdwinChilvers

Faculty of Medicine, National Heart & Lung Institute

Emeritus Professor of Medicine
 
 
 
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Contact

 

+44 (0)20 7594 5570e.chilvers

 
 
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Assistant

 

Miss Dawn Burby +44 (0)20 7594 6581

 
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Location

 

540ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bashant:2021:10.1136/annrheumdis-2020-218338,
author = {Bashant, KR and Aponte, AM and Randazzo, D and Rezvan, Sangsari P and Wood, AJ and Bibby, JA and West, EE and Vassallo, A and Manna, ZG and Playford, MP and Jordan, N and Hasni, S and Gucek, M and Kemper, C and Conway, Morris A and Morgan, NY and Toepfner, N and Guck, J and Mehta, NN and Chilvers, ER and Summers, C and Kaplan, MJ},
doi = {10.1136/annrheumdis-2020-218338},
journal = {Annals of the Rheumatic Diseases},
pages = {209--218},
title = {Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus},
url = {http://dx.doi.org/10.1136/annrheumdis-2020-218338},
volume = {80},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - OBJECTIVES: Low-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking and immune function are intimately linked to cellular biophysical properties. This study used proteomic, biomechanical and functional analyses to further define neutrophil heterogeneity in the context of SLE. METHODS: Proteomic/phosphoproteomic analyses were performed in healthy control (HC) normal density neutrophils (NDNs), SLE NDNs and autologous SLE LDGs. The biophysical properties of these neutrophil subsets were analysed by real-time deformability cytometry and lattice light-sheet microscopy. A two-dimensional endothelial flow system and a three-dimensional microfluidic microvasculature mimetic (MMM) were used to decouple the contributions of cell surface mediators and biophysical properties to neutrophil trafficking, respectively. RESULTS: Proteomic and phosphoproteomic differences were detected between HC and SLE neutrophils and between SLE NDNs and LDGs. Increased abundance of type 1 interferon-regulated proteins and differential phosphorylation of proteins associated with cytoskeletal organisation were identified in SLE LDGs relative to SLE NDNs. The cell surface of SLE LDGs was rougher than in SLE and HC NDNs, suggesting membrane perturbances. While SLE LDGs did not display increased binding to endothelial cells in the two-dimensional assay, they were increasingly retained/trapped in the narrow channels of the lung MMM. CONCLUSIONS: Modulation of the neutrophil proteome and distinct changes in biophysical properties are observed alongside differences in neutrophil trafficking. SLE LDGs may be increasingly retained in microvasculature networks, which has important pathogenic implications in the context of lupus organ damage and small vessel vasculopathy.
AU  - Bashant,KR
AU  - Aponte,AM
AU  - Randazzo,D
AU  - Rezvan,Sangsari P
AU  - Wood,AJ
AU  - Bibby,JA
AU  - West,EE
AU  - Vassallo,A
AU  - Manna,ZG
AU  - Playford,MP
AU  - Jordan,N
AU  - Hasni,S
AU  - Gucek,M
AU  - Kemper,C
AU  - Conway,Morris A
AU  - Morgan,NY
AU  - Toepfner,N
AU  - Guck,J
AU  - Mehta,NN
AU  - Chilvers,ER
AU  - Summers,C
AU  - Kaplan,MJ
DO  - 10.1136/annrheumdis-2020-218338
EP  - 218
PY  - 2021///
SN  - 0003-4967
SP  - 209
TI  - Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus
T2  - Annals of the Rheumatic Diseases
UR  - http://dx.doi.org/10.1136/annrheumdis-2020-218338
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32988843
UR  - https://ard.bmj.com/content/80/2/209
UR  - http://hdl.handle.net/10044/1/83010
VL  - 80
ER  -
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