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. 2007 Jan 1;178(1):530-8.
doi: 10.4049/jimmunol.178.1.530.

C-reactive Protein-Mediated Suppression of Nephrotoxic Nephritis: Role of Macrophages, Complement, and Fcgamma Receptors

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C-reactive Protein-Mediated Suppression of Nephrotoxic Nephritis: Role of Macrophages, Complement, and Fcgamma Receptors

Wilfredo Rodriguez et al. J Immunol. .
Free article

Abstract

C-reactive protein (CRP) is a member of the pentraxin family of proteins and an acute phase reactant. CRP modulates the response to inflammatory stimuli including LPS and C5a. We recently demonstrated that CRP prevents and reverses proteinuria in accelerated nephrotoxic nephritis (NTN). NTN is a model of active inflammatory immune complex-mediated nephritis induced by injection of antiglomerular basement membrane. CRP treatment prevented the induction of NTN in C57BL/6 (B6) mice, increased survival, and reversed ongoing nephritis. Protection was associated with a decrease in IL-1beta and chemokines in the kidney and peritoneal cells as measured by quantitative RT-PCR. However, IL-10(-/-) mice were not protected by CRP either when given before disease onset or when disease activity was maximal. FcgammaRI(-/-) mice developed NTN, but were only transiently protected by CRP treatment. This transient protection was abrogated by cobra venom factor depletion of complement from FcgammaRI(-/-) mice. However, complement depletion did not prevent CRP-mediated protection in B6 mice, and CRP was protective in C3(-/-) mice. The role of macrophages in the protection provided by CRP was tested by treating B6 mice with liposomes containing clodronate. Clodronate-containing liposomes deplete mice of splenic and hepatic macrophages for 5-7 days. Pretreatment of NTN mice with clodronate but not control liposomes completely prevented CRP-mediated protection. These studies suggest that CRP mediates protection from NTN through the induction of IL-10 and that macrophages are required. In addition, FcgammaRI plays an important role but is not the sole mediator of CRP-mediated protection.

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