English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus

MPS-Authors
/persons/resource/persons241284

Guck,  Jochen
Guck Division, Max Planck Institute for the Science of Light, Max Planck Society;
Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Bashant, K. R., Aponte, A. M., Randazzo, D., Sangsari, P. R., Wood, A. J. T., Bibby, J. A., et al. (2020). Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus. Annals of the Rheumatic Diseases, 80(2), 209-218. doi:10.1136/annrheumdis-2020-218338.


Cite as: http://hdl.handle.net/21.11116/0000-0007-D175-9
Abstract
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.