| Autor: |
Mark E. T. Penfold, Ronald J. Falk, Juan C. Jaen, Lin Gan, Daniel J. Dairaghi, Bao Lu, Thomas J. Schall, Lisa Seitz, Peiqi Hu, Craig Gerard, J. Charles Jennette, Norma P. Gerard, Hong Xiao, Yu Wang, Trageen Baumgart, Jay P. Powers, Linda S. Ertl |
| Rok vydání: |
2014 |
| Předmět: |
|
| Zdroj: |
Journal of the American Society of Nephrology. 25:225-231 |
| ISSN: |
1046-6673 |
| Popis: |
Necrotizing and crescentic GN (NCGN) with a paucity of glomerular immunoglobulin deposits is associated with ANCA. The most common ANCA target antigens are myeloperoxidase (MPO) and proteinase 3. In a manner that requires activation of the alternative complement pathway, passive transfer of antibodies to mouse MPO (anti-MPO) induces a mouse model of ANCA NCGN that closely mimics human disease. Here, we confirm the importance of C5aR/CD88 in the mediation of anti-MPO–induced NCGN and report that C6 is not required. We further demonstrate that deficiency of C5a-like receptor (C5L2) has the reverse effect of C5aR/CD88 deficiency and results in more severe disease, indicating that C5aR/CD88 engagement enhances inflammation and C5L2 engagement suppresses inflammation. Oral administration of CCX168, a small molecule antagonist of human C5aR/CD88, ameliorated anti-MPO–induced NCGN in mice expressing human C5aR/CD88. These observations suggest that blockade of C5aR/CD88 might have therapeutic benefit in patients with ANCA-associated vasculitis and GN. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
