title: Anti-C5a complementary peptide ameliorates acute peritoneal injury induced by neutralization of Crry and CD59.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mizuno
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuno
authors.forename: Masaki
authors.initials: M
authors.lastname: Imai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Mayu
authors.initials: M
authors.lastname: Kushida
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Noda
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Hidechika
authors.initials: H
authors.lastname: Okada
authors.forename: Noriko
authors.initials: N
authors.lastname: Okada
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism*; D018957:CD59 Antigens / Q000378:metabolism*; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D008297:Male; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D010530:Peritoneal Dialysis / Q000379:methods; D010537:Peritoneum / Q000187:drug effects* / Q000276:immunology / Q000293:injuries; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D000906:Antibodies; D000953:Antigens, Protozoan; D000954:Antigens, Surface; C118805:C5 phagosomal antigen, Paramecium multimicronucleatum; D018957:CD59 Antigens; C513105:Cr1l protein, rat; D010446:Peptide Fragments; D011956:Receptors, Cell Surface
keywords: C5a; complement; peritoneal dialysis; peritoneal injury; peritonitis