1 research outputs found
Extracellular vesicles from pristane-treated CD38-deficient mice express an antiinflammatory neutrophil protein signature, which reflects the mild lupus severity elicited in these mice
In CD38-deficient (Cd38-/-) mice intraperitoneal injection of pristane induces a
lupus-like disease, which is milder than that induced in WT mice, showing
significant differences in the inflammatory and autoimmune processes
triggered by pristane. Extracellular vesicles (EV) are present in all body fluids.
Shed by cells, their molecular make-up reflects that of their cell of origin and/or
tissue pathological situation. The aim of this study was to analyze the protein
composition, protein abundance, and functional clustering of EV released by
peritoneal exudate cells (PECs) in the pristane experimental lupus model, to
identify predictive or diagnostic biomarkers that might discriminate the
autoimmune process in lupus from inflammatory reactions and/or normal
physiological processes. In this study, thanks to an extensive proteomic
analysis and powerful bioinformatics software, distinct EV subtypes were identified in the peritoneal exudates of pristane-treated mice: 1) small EV
enriched in the tetraspanin CD63 and CD9, which are likely of exosomal
origin; 2) small EV enriched in CD47 and CD9, which are also enriched in
plasma-membrane, membrane-associated proteins, with an ectosomal origin;
3) small EV enriched in keratins, ECM proteins, complement/coagulation
proteins, fibrin clot formation proteins, and endopetidase inhibitor proteins.
This enrichment may have an inflammation-mediated mesothelial-tomesenchymal
transition origin, representing a protein corona on the surface
of peritoneal exudate EV; 4) HDL-enriched lipoprotein particles. Quantitative
proteomic analysis allowed us to identify an anti-inflammatory, Annexin A1-
enriched pro-resolving, neutrophil protein signature, which was more
prominent in EV from pristane-treated Cd38-/- mice, and quantitative
differences in the protein cargo of the ECM-enriched EV from Cd38-/- vs WT
mice. These differences are likely to be related with the distinct inflammatory
outcome shown by Cd38-/- vs WT mice in response to pristane treatment. Our
results demonstrate the power of a hypothesis-free and data-driven approach
to transform the heterogeneity of the peritoneal exudate EV from pristanetreated
mice in valuable information about the relative proportion of different
EV in a given sample and to identify potential protein markers specific for the
different small EV subtypes, in particular those proteins defining EV involved in
the resolution phase of chronic inflammation.Proyecto del plan estatal, Ministerio de Ciencia e Innovacion PT13/0001/011CSIC PT17/0019/0010
PID2020-119567RB-I0