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Infection and Immunity, March 2007, p. 1229-1236, Vol. 75, No. 3
0019-9567/07/$08.00+0     doi:10.1128/IAI.01663-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Monocyte Chemoattractant Protein 1, Macrophage Inflammatory Protein 1, and RANTES Recruit Macrophages to the Kidney in a Mouse Model of Hemolytic-Uremic Syndrome

Division of Nephrology, University of Virginia, Box 800133, 1 Lane Road OMS 5815, Charlottesville, Virginia 22903

Received 17 October 2006/ Returned for modification 22 November 2006/ Accepted 22 December 2006

The macrophage has previously been implicated in contributing to the renal inflammation associated with hemolytic-uremic syndrome (HUS). However, there is currently no in vivo model detailing the contribution of the renal macrophage to the kidney disease associated with HUS. Therefore, renal macrophage recruitment and inhibition of infiltrating renal macrophages were evaluated in an established HUS mouse model. Macrophage recruitment to the kidney was evident by immunohistochemistry 2 h after administration of purified Stx2 and peaked at 48 h postinjection. Mice administered a combination of Stx2 and lipopolysaccharide (LPS) showed increased macrophage recruitment to the kidney compared to mice treated with Stx2 or LPS alone. Monocyte chemoattractants were induced in the kidney, including monocyte chemoattractant protein 1 (MCP-1/CCL2), macrophage inflammatory protein 1 (MIP-1/CCL3), and RANTES (CCL5), in a pattern that was coincident with macrophage infiltration as indicated by immunohistochemistry, protein, and RNA analyses. MCP-1 was the most abundant chemokine, MIP-1 was the least abundant, and RANTES levels were intermediate. Mice treated with MCP-1, MIP-1, and RANTES neutralizing antibodies had a significant decrease in Stx2 plus LPS-induced macrophage accumulation in the kidney, indicating that these chemokines are required for macrophage recruitment. Furthermore, mice exposed to these three neutralizing antibodies had decreased fibrin deposition in their kidneys, implying that macrophages contribute to the renal damage associated with HUS.

Published ahead of print on 12 January 2007.

Editor: A. D. O'Brien

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