Neutrophils Clear Circulating Apoptotic Cell Derived Extracellular Vesicles and Secrete Pro-Regenerative Factors after Liver Resection

Background: Inflammatory processes relying on intrahepatic neutrophil accumulation predominate the priming phase of liver regeneration. During later stages relevance neutrophils remains incompletely understood. Here we aimed to investigate dynamic phenotypical changes circulating upon stimulation with apoptotic cell derived extracellular vesicles (aEV) and their potential role in human Methods: 93 patients undergoing resection were included this study. Dynamic perioperative aEV, caspase cleaved cytokeratin 18 (M30), M65 HGF assessed. In vitro efferocytosis aEV by was assessed image flow cytometry. Secreted proteins measured using a multiplex bead array assay. Results: M30 increased transiently at POD1 full recovery function. Patients who developed dysfunction failed increase M30. Neutrophils engulf efficiently, which associated expression CD11b, CD16, CD66b, CD62L shedding, but neither induced NETosis, respiratory burst, or degranulation. While bacterial lead an inflammatory phenotype, engulfment reduced secretion pro-inflammatory cytokines could not inhibit activation co-cultured T cells. Circulating levels correlated levels. Conclusion: translocation, occurring during regeneration, shifts towards shed regeneration are engulfed leading non-inflammatory, non-immunosuppressive polarization state tissue repair phenotype indicating switch