title: Specific collaboration between rat membrane complement regulators Crry and CD59 protects peritoneum from damage by autologous complement activation.
abstract: BACKGROUND
  The peritoneal cavity is isolated from the outside and is usually a sterile environment. Patients on peritoneal dialysis (PD) have PD fluid (PDF) infused into the peritoneal cavity. We previously showed that unregulated complement activation could contribute to the development of peritoneal inflammation in yeast peritonitis in PD therapy. In that situation, suppression of local complement activation is essential to protect the host from further injury. The membrane complement regulators (CRegs), Crry, CD55 and CD59, are expressed in the rat peritoneum, especially along the mesothelial cell layer.
  
  
  METHODS
  We investigated CRegs' functional roles in the peritoneal cavity using blocking mAb against each CReg and complement activation in different PDFs.
  
  
  RESULTS
  Blockade of any single CReg did not cause spontaneous peritoneal injury in rat. Combined blockade of Crry and CD59 induced focal peritoneal tissue injury and heavy accumulation of inflammatory cells with peritoneal edema at 24 h. Deposits of C3 and C5b-9 were found on the peritoneal surface after combined blocking of Crry and CD59. Systemic complement depletion by cobra venom factor abrogated these inflammatory changes. When combined blockade of Crry and CD59 was performed with PDF of different pH and glucose concentration in rats, the peritoneal injuries were enhanced with lower pH and higher glucose concentration. These results were confirmed by in vitro experiments using primary rat mesothelial cell culture.
  
  
  CONCLUSIONS
  Rat CRegs, Crry and CD59, specifically collaborate to control complement activation in rat peritoneum. During PD, impairment of CReg might contribute to the development of severe peritoneal inflammation.
authors.affiliation: Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mizuno
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuno
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Noda
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Noriko
authors.initials: N
authors.lastname: Okada
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yuzawa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D018958:CD55 Antigens / Q000378:metabolism; D018957:CD59 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D004487:Edema / Q000517:prevention & control*; D004848:Epithelium; D007124:Immunoenzyme Techniques; D008297:Male; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D018958:CD55 Antigens; D018957:CD59 Antigens; D003176:Complement C3; D015938:Complement Membrane Attack Complex; C513105:Cr1l protein, rat; D011956:Receptors, Cell Surface