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Characterizing Salmonella Typhimurium-induced Septic Peritonitis in Mice
Published on: July 29, 2022
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
Abstract:
Fungal peritonitis is an important complication in peritoneal dialysis patients; either continuous or recurrent peritonitis may enhance peritoneal damage. Even when the peritoneal dialysis catheter is removed in patients with fungal peritonitis, peritoneal fibrosis can progress and evolve into encapsular peritoneal sclerosis. It is unclear why fungal infections are worse than bacterial in these respects. Zymosan is a cell wall component of yeast that strongly activates the complement system. In this study, we compared the effects of zymosan and bacterial LPS on peritoneal inflammation in a rat peritoneal injury model induced by mechanical scraping. Intraperitoneal administration of zymosan, but not LPS or vehicle, caused markedly enhanced peritonitis with massive infiltration of cells and deposition of complement activation products C3b and membrane attack complex on day 5. In rats administered zymosan and sacrificed on days 18 or 36, peritoneal inflammation persisted with accumulation of ED-1-positive cells, small deposits of C3b and membrane attack complex, exudation of fibrinogen, and capillary proliferation in subperitoneal tissues. When zymosan was administered daily for 5 days after peritoneal scrape, there was even greater peritoneal inflammation with peritoneal thickening, inflammatory cell accumulation, and complement deposition. Inhibition of systemic complement by pretreatment with cobra venom factor or local inhibition by i.p. administration of the recombinant complement regulator Crry-Ig reduced peritoneal inflammation in zymosan-treated rats. Our results show that yeast components augment inflammation in the injured peritoneum by causing complement activation within the peritoneal cavity. Local anticomplement therapy may therefore protect from peritoneal damage during fungal infection of the peritoneum.
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.
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