The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells

Abstract

Pretreatment with synthetic C-reactive protein (CRP), a functional CRP peptide, has the potential to augment macrophage phagocytosis by bacterial challenge. However, the posttreatment is clinically ideal. We investigated the efficacy of posttreatment with synthetic CRP on murine cecal ligation and puncture (CLP), focusing on liver macrophages. Mice received CLP, and 1 h later, synthetic CRP or saline was intraperitoneally administered. Posttreatment with synthetic CRP increased the murine survival after CLP. It reduced viable bacterial counts in the liver 24 h after CLP with an increase in the number of Kupffer cells but not monocyte-derived liver macrophages. Posttreatment with synthetic CRP increased the phagolytic activity of Kupffer cells against Escherichia coli (E. coli) as well as capsulated Klebsiella pneumoniae at 3 h after CLP. Synthetic CRP therapy augmented TNF production by E. coli-phagocytosing Kupffer cells, resulting in an increase in tissue TNF levels in the liver at 24 h. Kupffer cells substantially expressed FcγRI, which is a ligand of CRP, and their FcγRI expression was further increased after CLP. In contrast, synthetic CRP therapy affected neither the phagocytic function of monocyte-derived liver macrophages (showing a weak FcγRI expression) nor their TNF production. Depletion of Kupffer cells in mice inhibited these beneficial effects of synthetic CRP in CLP mice. Conclusion: Posttreatment with synthetic CRP effectively improves murine bacterial peritonitis via the activation of phagocytosis of FcγRI-expressing Kupffer cells.