PMID- 21098015 OWN - NLM STAT- MEDLINE DCOM- 20110930 LR - 20191224 IS - 1460-2385 (Electronic) IS - 0931-0509 (Linking) VI - 26 IP - 6 DP - 2011 Jun TI - Specific collaboration between rat membrane complement regulators Crry and CD59 protects peritoneum from damage by autologous complement activation. PG - 1821-30 LID - 10.1093/ndt/gfq683 [doi] AB - 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. FAU - Mizuno, Tomohiro AU - Mizuno T AD - Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan. FAU - Mizuno, Masashi AU - Mizuno M FAU - Morgan, B Paul AU - Morgan BP FAU - Noda, Yukihiro AU - Noda Y FAU - Yamada, Kiyofumi AU - Yamada K FAU - Okada, Noriko AU - Okada N FAU - Yuzawa, Yukio AU - Yuzawa Y FAU - Matsuo, Seiichi AU - Matsuo S FAU - Ito, Yasuhiko AU - Ito Y LA - eng GR - 068590/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101122 PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Antigens, Surface) RN - 0 (CD55 Antigens) RN - 0 (CD59 Antigens) RN - 0 (Complement C3) RN - 0 (Complement Membrane Attack Complex) RN - 0 (Cr1l protein, rat) RN - 0 (Receptors, Cell Surface) SB - IM MH - Animals MH - Antigens, Surface/*metabolism MH - CD55 Antigens/metabolism MH - CD59 Antigens/*metabolism MH - Cells, Cultured MH - *Complement Activation MH - Complement C3/*metabolism MH - Complement Membrane Attack Complex/*metabolism MH - Edema/*prevention & control MH - Epithelium MH - Immunoenzyme Techniques MH - Male MH - Peritoneal Dialysis MH - Peritoneum/injuries/*metabolism/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Cell Surface/*metabolism EDAT- 2010/11/26 06:00 MHDA- 2011/10/01 06:00 CRDT- 2010/11/25 06:00 PHST- 2010/11/25 06:00 [entrez] PHST- 2010/11/26 06:00 [pubmed] PHST- 2011/10/01 06:00 [medline] AID - gfq683 [pii] AID - 10.1093/ndt/gfq683 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2011 Jun;26(6):1821-30. doi: 10.1093/ndt/gfq683. Epub 2010 Nov 22.