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Anti-C5a complementary peptide mitigates zymosan-induced severe peritonitis with fibrotic encapsulation in rats

Daiki Iguchi1, Masashi Mizuno1,2, Yasuhiro Suzuki1,2

  • 1Nephrology, Nagoya University Graduate School of Medicine , Nagoya , Japan.

American Journal of Physiology. Renal Physiology
|October 4, 2018
PubMed

Insights

Complement activation contributes to peritoneal encapsulation in a rat model. An anti-C5a peptide (AcPepA) demonstrated therapeutic potential in treating fungal peritonitis and preventing fibrosis.

Area of Science:

  • Nephrology
  • Immunology
  • Pathology

Background:

  • Previous studies linked complement (C) to fungal peritonitis but didn't fully replicate human encapsular peritoneal sclerosis (EPS).
  • Existing models using zymosan (Zy) induced parietal, not visceral, peritoneal injury.

Purpose of the Study:

  • To investigate the role of complement in visceral peritoneal fibrous encapsulation.
  • To evaluate the therapeutic efficacy of an anti-C5a peptide (AcPepA) in a novel rat model of fungal peritonitis.

Main Methods:

  • A rat model of zymosan and methylglyoxal (Zy/MGO)-induced peritonitis was established to mimic EPS.
  • Peritoneal injury, inflammation, and complement deposition (C3b, C5b-9) were assessed.
  • The effects of AcPepA treatment on peritoneal changes and fibrosis were evaluated.

Main Results:

  • Zy/MGO peritonitis induced significant peritoneal thickening, inflammation, and complement deposition.
  • Fibrous encapsulation of the visceral peritoneum, characteristic of EPS, was observed by day 14.
  • AcPepA treatment significantly ameliorated peritoneal injury and fibrous changes, even when administered post-induction.

Conclusions:

  • Complement component C5a appears to play a crucial role in the development of visceral peritoneal encapsulation.
  • AcPepA shows therapeutic promise for fungal peritonitis by mitigating inflammation and preventing subsequent peritoneal fibrosis.
Keywords:
C5acomplementencapsular peritoneal sclerosisfungusperitoneal dialysis

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