Innate immune profiling discriminates between liver regeneration and liver failure following partial hepatectomy

Abstract

Abstract Post-hepatectomy liver failure is a major complication following liver resection and while the basic mechanisms are not well understood, limited regeneration of the remnant tissue contributes to its development. Using an established murine model of 70% partial hepatectomy, we studied the innate immunological profile associated with liver regeneration and liver failure. Following partial hepatectomy, there is a significant increase in circulating CD11b+ myeloid derived cells from (52±10 to 70±12 p>0.01). Further characterization of the CD11b+ cells revealed three different subpopulations: Gr-1hiF4/80, Gr-1hiF4/80+, and Gr-1loF4/80+. Liver failure was accompanying with markedly prolonged and increased mobilization and liver infiltration of activated CD11b+ cells (6±2% on day 0 to 55±12% on day 1 p>0.001). Specifically, the CD11b+Gr-1hiF4/80− cells identified as neutrophils were predominantly increased in these mice from (25±5% to 80±10% p>0.001) on day 1. And persistently remained high until day 7. We also found high IL-6 serum levels in these mice (300±150pg/mL) on day 1. The other CD11b+ cell populations, including Gr-1hiF4/80+ and Gr-1loF4/80+ cells, were markedly reduced in peripheral blood of mice with impaired liver regeneration. In contrast, all CD11b+ populations rapidly recovered to normal levels within 2 days in mice showing normal liver regeneration. In conclusion, following partial hepatectomy, significantly prolonged infiltration of CD11b+ neutrophils and marked reduction of other CD11b+ populations are a hallmark of liver failure. Thus, controlling neutrophil infiltration/activation may help ease recovery from the surgical procedure and improve liver regeneration after partial liver resection.