Zymosan, but not lipopolysaccharide, triggers severe and progressive peritoneal injury accompanied by complement

Masashi Mizuno1, Yasuhiko Ito, Natalie Hepburn

  • 1Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan. mmizu@med.nagoya-u.ac.jp

Insights

Yeast components, like zymosan, worsen peritoneal inflammation and damage in dialysis patients by activating the complement system. Local anticomplement therapy may prevent this peritoneal damage during fungal infections.

Area of Science:

  • Immunology
  • Nephrology
  • Pathology

Background:

  • Fungal peritonitis is a serious complication for peritoneal dialysis patients, potentially leading to peritoneal fibrosis and encapsular peritoneal sclerosis.
  • The mechanisms by which fungal infections cause more severe peritoneal damage than bacterial infections remain unclear.
  • Zymosan, a yeast cell wall component, is known to strongly activate the complement system.

Purpose of the Study:

  • To compare the effects of zymosan (yeast component) and bacterial lipopolysaccharide (LPS) on peritoneal inflammation in a rat model.
  • To investigate the role of complement activation in zymosan-induced peritoneal inflammation and damage.
  • To evaluate the potential of anticomplement therapy in mitigating peritoneal injury.

Main Methods:

  • A rat model of peritoneal injury was induced by mechanical scraping.
  • Intraperitoneal administration of zymosan, LPS, or vehicle was performed.
  • Peritoneal inflammation, cell infiltration, complement deposition (C3b, membrane attack complex), fibrinogen exudation, and capillary proliferation were assessed.
  • Systemic complement inhibition (cobra venom factor) and local complement inhibition (Crry-Ig) were used to evaluate therapeutic effects.

Main Results:

  • Zymosan administration, unlike LPS or vehicle, induced significant peritonitis with massive cell infiltration and complement deposition.
  • Chronic administration of zymosan led to persistent peritoneal inflammation, characterized by inflammatory cell accumulation and complement deposition.
  • Both systemic and local anticomplement therapies significantly reduced peritoneal inflammation in zymosan-treated rats.

Conclusions:

  • Yeast components, such as zymosan, exacerbate peritoneal inflammation in injured tissue by activating the complement system within the peritoneal cavity.
  • Complement activation plays a critical role in the pathogenesis of fungal peritonitis-associated peritoneal damage.
  • Local anticomplement therapy presents a potential therapeutic strategy to protect against peritoneal damage in cases of fungal peritonitis.