title: Zymosan, but not lipopolysaccharide, triggers severe and progressive peritoneal injury accompanied by complement activation in a rat peritonitis model.
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.
authors: Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan. mmizu@med.nagoya-u.ac.jp
authors: Masashi
authors: M
authors: Mizuno
authors: Yasuhiko
authors: Y
authors: Ito
authors: Natalie
authors: N
authors: Hepburn
authors: Tomohiro
authors: T
authors: Mizuno
authors: Yukihiro
authors: Y
authors: Noda
authors: Yukio
authors: Y
authors: Yuzawa
authors: Claire L
authors: CL
authors: Harris
authors: B Paul
authors: BP
authors: Morgan
authors: Seiichi
authors: S
authors: Matsuo
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003167:Complement Activation; D003179:Complement C3b; D015938:Complement Membrane Attack Complex; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009389:Neovascularization, Pathologic; D010537:Peritoneum / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology; D010538:Peritonitis / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015003:Yeasts / Q000737:chemistry; D015054:Zymosan / Q000009:adverse effects*
chemical_list: D015938:Complement Membrane Attack Complex; D008070:Lipopolysaccharides; D003179:Complement C3b; D015054:Zymosan