PMID- 23904221 OWN - NLM STAT- MEDLINE DCOM- 20140210 LR - 20191224 IS - 1522-1466 (Electronic) IS - 1522-1466 (Linking) VI - 305 IP - 11 DP - 2013 Dec 1 TI - Anti-C5a complementary peptide ameliorates acute peritoneal injury induced by neutralization of Crry and CD59. PG - F1603-16 LID - 10.1152/ajprenal.00681.2012 [doi] AB - In peritoneal dialysis (PD) therapy, physical stresses such as exposure to peritoneal dialysate, catheter trauma, and peritonitis may induce peritoneal injury that can prevent continued long-term PD therapy. Therefore, protection of the peritoneum is an important target to enable long-term PD therapy in patients with end-stage renal disease. We previously showed that neutralization of the membrane complement regulators (CRegs) Crry and CD59 in rat peritoneum provokes development of acute peritoneal injury due to uncontrolled complement activation. C5a is a key effecter molecule of the complement system released during acute inflammation. Control of C5a has been proposed as a strategy to suppress inflammatory reactions and, because peritoneal injury is accompanied by inflammation, we hypothesized that C5a targeted therapy might be an effective way to suppress peritoneal injury. In the present study we used an established acute peritonitis model induced by neutralization of CRegs to investigate the effects on acute peritoneal injury of inhibiting C5a. Intravenous administration of an anti-C5a complementary peptide (AcPepA) up to 4 h after induction of injury significantly and dose-dependently prevented accumulation of inflammatory cells and reduced tissue damage in the model, accompanied by decreased C3b deposition. We show that C5a contributed to the development of peritoneal injury. Our results suggest that C5a is a target for preventing or treating peritoneal injury in patients undergoing prolonged PD therapy or with infectious complications. FAU - Mizuno, Tomohiro AU - Mizuno T AD - Renal Replacement Therapy, Division of Nephrology, Nagoya Univ. Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan. mmizu@med.nagoya-u.ac.jp or masashim1jp@yahoo.co.jp. FAU - Mizuno, Masashi AU - Mizuno M FAU - Imai, Masaki AU - Imai M FAU - Suzuki, Yasuhiro AU - Suzuki Y FAU - Kushida, Mayu AU - Kushida M FAU - Noda, Yukihiro AU - Noda Y FAU - Maruyama, Shoichi AU - Maruyama S FAU - Okada, Hidechika AU - Okada H FAU - Okada, Noriko AU - Okada N FAU - Matsuo, Seiichi AU - Matsuo S FAU - Ito, Yasuhiko AU - Ito Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130731 PL - United States TA - Am J Physiol Renal Physiol JT - American journal of physiology. Renal physiology JID - 100901990 RN - 0 (Antibodies) RN - 0 (Antigens, Protozoan) RN - 0 (Antigens, Surface) RN - 0 (C5 phagosomal antigen, Paramecium multimicronucleatum) RN - 0 (CD59 Antigens) RN - 0 (Cr1l protein, rat) RN - 0 (Peptide Fragments) RN - 0 (Receptors, Cell Surface) SB - IM MH - Animals MH - Antibodies/immunology/*therapeutic use MH - Antigens, Protozoan/*immunology MH - Antigens, Surface/*immunology/*metabolism MH - CD59 Antigens/*metabolism MH - Complement Activation/drug effects/immunology MH - Disease Models, Animal MH - Male MH - Peptide Fragments/immunology/pharmacology MH - Peritoneal Dialysis/methods MH - Peritoneum/*drug effects/immunology/injuries MH - Peritonitis/chemically induced/*drug therapy/immunology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Cell Surface/*metabolism OTO - NOTNLM OT - C5a OT - complement OT - peritoneal dialysis OT - peritoneal injury OT - peritonitis EDAT- 2013/08/02 06:00 MHDA- 2014/02/11 06:00 CRDT- 2013/08/02 06:00 PHST- 2013/08/02 06:00 [entrez] PHST- 2013/08/02 06:00 [pubmed] PHST- 2014/02/11 06:00 [medline] AID - ajprenal.00681.2012 [pii] AID - 10.1152/ajprenal.00681.2012 [doi] PST - ppublish SO - Am J Physiol Renal Physiol. 2013 Dec 1;305(11):F1603-16. doi: 10.1152/ajprenal.00681.2012. Epub 2013 Jul 31.