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Am J Pathol. 2012 Mar;180(3):1040-8. doi: 10.1016/j.ajpath.2011.11.011. Epub 2011 Dec 25.

Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome.

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  • 1Division of Immunology, Institute of Experimental Medicine (IMEX-CONICET), National Academy of Medicine, Buenos Aires, Argentina. mvramos@hematologia.anm.edu

Abstract

Shiga toxin (Stx)-producing Escherichia coli is the main etiological agent that causes hemolytic uremic syndrome (HUS), a microangiopathic disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Although direct cytotoxic effects on endothelial cells by Stx are the primary pathogenic event, there is evidence that indicates the inflammatory response mediated by polymorphonuclear neutrophils and monocytes as the key event during HUS development. Because the chemokine receptor CCR1 participates in the pathogenesis of several renal diseases by orchestrating myeloid cell kidney infiltration, we specifically addressed the contribution of CCR1 in a murine model of HUS. We showed that Stx type 2-treated CCR1(-/-) mice have an increased survival rate associated with less functional and histological renal damage compared with control mice. Stx type 2-triggered neutrophilia and monocytosis and polymorphonuclear neutrophil and monocyte renal infiltration were significantly reduced and delayed in CCR1(-/-) mice compared with control mice. In addition, the increase of the inflammatory cytokines (tumor necrosis factor-α and IL-6) in plasma was delayed in CCR1(-/-) mice compared with control mice. These data demonstrate that CCR1 participates in cell recruitment to the kidney and amplification of the inflammatory response that contributes to HUS development. Blockade of CCR1 could be important to the design of future therapies to restrain the inflammatory response involved in the development of HUS.

Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PMID:
22203055
[PubMed - indexed for MEDLINE]
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