Molecular and cellular profiles of the resolution phase in a damage-associated molecular pattern (DAMP)-mediated peritonitis model and revelation of leukocyte persistence in peritoneal tissues

FASEB J. 2015 May;29(5):1914-29. doi: 10.1096/fj.14-259341. Epub 2015 Jan 21.


Models of microbe-elicited peritonitis have been invaluable to identify mechanisms underlying inflammation resolution, but whether resolution mechanisms differ from an inflammatory agent to another has not been determined. Thus, we analyzed the cellular and molecular components of the resolution phase of non-microbe-induced inflammation. In thioglycollate (TG)-induced peritonitis, resolution started at 12 h (Tmax) and displayed a 22 h resolution interval (Ri). During resolution, lipoxin A4, resolvin (Rv) D1 and RvD2, protectin D1 (PD1), and maresin 1 (MaR1) were transiently produced while RvD5 was continually generated. In addition, docosahexaenoic acid (DHA)-derived mediators were produced to a higher extent than in microbial peritonitis. We also investigated leukocyte infiltration and clearance in peritoneal tissues surrounding the inflammatory site. In the omentum, resolution parameters, neutrophil apoptosis, and efferocytosis were similar to those of the peritoneal cavity. However, we noticed long-term persistence of M2-polarized macrophages and B-lymphocytes in the omentum after TG administration, whereas zymosan injection caused M1/M2-macrophage and T-lymphocyte persistence regardless of the magnitude of the inflammatory response. Our study indicates that some aspects of resolution are shaped in a stimulus-specific manner, and it ultimately argues that the tissues surrounding the inflammatory site must also be considered to address the inflammatory response globally.

Keywords: bioactive lipid mediators; macrophage polarization; omentum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Blotting, Western
  • Cells, Cultured
  • Docosahexaenoic Acids / genetics
  • Docosahexaenoic Acids / metabolism
  • Female
  • Flow Cytometry
  • Immunoenzyme Techniques
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Leukocytes / immunology*
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Lipids / analysis
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Omentum / immunology
  • Omentum / metabolism
  • Omentum / pathology
  • Peritonitis / chemically induced
  • Peritonitis / immunology*
  • Peritonitis / metabolism*
  • Phagocytosis / physiology
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thioglycolates / toxicity*
  • Zymosan / toxicity


  • Lipids
  • RNA, Messenger
  • Thioglycolates
  • protectin D1
  • resolvin D1
  • Docosahexaenoic Acids
  • Zymosan