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C3a receptor deficiency accelerates the onset of renal injury in the MRL/lpr mouse.
- Source :
-
Molecular immunology [Mol Immunol] 2009 Apr; Vol. 46 (7), pp. 1397-404. Date of Electronic Publication: 2009 Jan 23. - Publication Year :
- 2009
-
Abstract
- The development and progression of systemic lupus erythematosus (SLE) is strongly associated with complement activation and deposition. The anaphylatoxin C3a is a product of complement activation with immunomodulatory properties, and the receptor for C3a (C3aR) is not only expressed by granulocytes and antigen presenting cell populations, but it is also strongly up-regulated in lupus prone mice with active nephritis. In order to characterize the role of the C3aR in inflammatory nephritis, we bred C3aR knock out mice onto the MRL/lpr genetic background (C3aR KO MRL). Compared to control MRL/lpr mice, C3aR KO MRL mice had elevated auto-antibody titers and an earlier onset of renal injury. At 8 weeks, renal expression of a wide range of chemokines and chemokine receptors was increased in C3aR KO MRL kidneys compared to controls. Only the expression of MCP-1 was significantly decreased in the C3aR KO MRL mice. The increased chemokine and chemokine receptor expression seen in the C3aR KO MRL mice was associated with a more rapid rise in serum creatinine and the acceleration of renal fibrosis. However, loss of the C3aR had little impact on long-term kidney injury and did not alter survival. These findings suggest that activation of the C3aR plays a protective, not pathologic, role in the early phase of inflammatory nephritis in the MRL/lpr model of SLE.
- Subjects :
- Animals
Disease Progression
Genetic Predisposition to Disease
Lupus Nephritis complications
Lupus Nephritis mortality
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Complement physiology
Survival Analysis
Time Factors
Lupus Nephritis genetics
Mice, Inbred MRL lpr
Receptors, Complement genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 46
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 19167760
- Full Text :
- https://doi.org/10.1016/j.molimm.2008.12.004