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Anti-C5a complementary peptide ameliorates acute peritoneal injury induced by neutralization of Crry and CD59
- Source :
- American Journal of Physiology-Renal Physiology. 305:F1603-F1616
- Publication Year :
- 2013
- Publisher :
- American Physiological Society, 2013.
-
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.
- Subjects :
- Male
Physiology
medicine.medical_treatment
Peritonitis
Antigens, Protozoan
CD59 Antigens
Receptors, Cell Surface
chemical and pharmacologic phenomena
Inflammation
CD59
Antibodies
Neutralization
Peritoneal dialysis
Targeted therapy
Rats, Sprague-Dawley
Peritoneum
medicine
Animals
Complement Activation
business.industry
medicine.disease
Peptide Fragments
Rats
Complement system
Disease Models, Animal
medicine.anatomical_structure
Antigens, Surface
Immunology
medicine.symptom
business
Peritoneal Dialysis
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 305
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi.dedup.....928f5ef4a7895f43635dec5c004be989