C3a receptor deficiency accelerates the onset of renal injury in the MRL/lpr mouse

Mol Immunol. 2009 Apr;46(7):1397-404. doi: 10.1016/j.molimm.2008.12.004. Epub 2009 Jan 23.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Progression
  • Genetic Predisposition to Disease
  • Lupus Nephritis / complications
  • Lupus Nephritis / genetics*
  • Lupus Nephritis / mortality
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr*
  • Mice, Knockout
  • Receptors, Complement / genetics*
  • Receptors, Complement / physiology
  • Survival Analysis
  • Time Factors


  • Receptors, Complement
  • complement C3a receptor