Specific collaboration between rat membrane complement regulators Crry and CD59 protects peritoneum from damage by autologous complement activation
Tomohiro Mizuno,Masashi Mizuno,B. Paul Morgan,Yukihiro Noda,Kiyofumi Yamada,Noriko Okada,Yukio Yuzawa,Seiichi Matsuo,Yasuhiko Ito +8 more
TL;DR: Rat CRegs, Crry and CD59, specifically collaborate to control complement activation in rat peritoneum as well as in vitro experiments using primary rat mesothelial cell culture.
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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.
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Citations
The Complement System in Dialysis: A Forgotten Story?
Felix Poppelaars,Bernardo Faria,Bernardo Faria,Mariana Gaya da Costa,Casper F. M. Franssen,Willem J. van Son,Stefan P Berger,Mohamed R. Daha,Marc A. Seelen +8 more
TL;DR: Results suggest that interventions targeting the complement system in dialysis could improve biocompatibility, dialysis efficacy, and long-term outcome.
Inflammation in peritoneal dialysis
Kar Neng Lai,Joseph Leung +1 more
TL;DR: The alteration in the peritoneal membrane will further be aggravated by peritonitis, advanced glycation end-products and glucose degradation products, and there are emerging new data supporting a pro-inflammatory role ofperitoneal adipocytes.
Membrane complement regulators protect against fibrin exudation increases in a severe peritoneal inflammation model in rats
Masashi Mizuno,Yasuhiko Ito,Tomohiro Mizuno,Claire L. Harris,Yasuhiro Suzuki,Noriko Okada,Seiichi Matsuo,B. Paul Morgan +7 more
TL;DR: The results show that complement activation in injured peritoneum drives peritoneal inflammation, and that enhancement of complement activation by inhibiting CReg and/or enhancing systemic activation contributes to the initiation of EPS; therefore, anti-complement agents might be of therapeutic value in humans for the treatment of EPS.
27
Atrial natriuretic peptide ameliorates peritoneal fibrosis in rat peritonitis model
Hiroshi Kato,Tomohiro Mizuno,Masashi Mizuno,Akiho Sawai,Yasuhiro Suzuki,Hiroshi Kinashi,Fumiko Nagura,Shoichi Maruyama,Yukihiro Noda,Kiyofumi Yamada,Seiichi Matsuo,Yasuhiko Ito +11 more
TL;DR: The results suggest that ANP is useful in preventing inflammation-induced peritoneal fibrosis and suppressed angiotensin II-induced upregulation of CTGF and PAI-1.
Transcriptional patterns in peritoneal tissue of encapsulating peritoneal sclerosis, a complication of chronic peritoneal dialysis.
Fabian R. Reimold,Fabian R. Reimold,Fabian R. Reimold,Niko Braun,Zsuzsanna K. Zsengellér,Isaac E. Stillman,S. Ananth Karumanchi,S. Ananth Karumanchi,Hakan R. Toka,Hakan R. Toka,Joerg Latus,Peter Fritz,Dagmar Biegger,Dagmar Biegger,Stephan Segerer,M. Dominik Alscher,Manoj Bhasin,Manoj Bhasin,Seth L. Alper,Seth L. Alper +19 more
TL;DR: A global transcriptome analysis of peritoneal tissue specimens from EPS patients, PD patients without EPS, and uremic patients without history of PD or EPS revealed distinct transcriptional patterns that discriminated these three clinical groups, compatible with the hypothesis that encapsulatingperitoneal sclerosis is a distinct pathological process from the simple peritoneAL fibrosis that accompanies all PD treatment.
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