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

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.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Wenderfer SE,Wang H,Ke B,Wetsel RA,Braun MC

doi

10.1016/j.molimm.2008.12.004

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

1397-404

issue

7

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(08)00774-8

journal_volume

46

pub_type

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