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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-28843

Lech, M; Avila-Ferrufino, A; Allam, R; Segerer, S; Khandoga, A; Krombach, F; Garlanda, C; Mantovani, A (2009). Resident dendritic cells prevent postischemic acute renal failure by help of single Ig IL-1 receptor-related protein. Journal of Immunology, 183(6):4109-4118.

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Abstract

Ischemia-reperfusion (IR) triggers tissue injury by activating innate immunity, for example, via TLR2 and TLR4. Surprisingly, TLR signaling in intrinsic renal cells predominates in comparison to intrarenal myeloid cells in the postischemic kidney. We hypothesized that immune cell activation is specifically suppressed in the postischemic kidney, for example, by single Ig IL-1-related receptor (SIGIRR). SIGIRR deficiency aggravated postischemic acute renal failure in association with increased renal CXCL2/MIP2, CCL2/MCP-1, and IL-6 mRNA expression 24 h after IR. Consistent with this finding interstitial neutrophil and macrophage counts were increased and tubular cell necrosis was aggravated in Sigirr-deficient vs wild-type IR kidneys. In vivo microscopy revealed increased leukocyte transmigration in the postischemic microvasculature of Sigirr-deficient mice. IL-6 and CXCL2/MIP2 release was much higher in Sigirr-deficient renal myeloid cells but not in Sigirr-deficient tubular epithelial cells after transient hypoxic culture conditions. Renal IR studies with chimeric mice confirmed this finding, as lack of SIGIRR in myeloid cells largely reproduced the phenotype of renal IR injury seen in Sigirr(-/-) mice. Additionally, clodronate depletion of dendritic cells prevented the aggravated renal failure in Sigirr(-/-) mice. Thus, loss of function mutations in the SIGIRR gene predispose to acute renal failure because SIGIRR prevents overshooting tissue injury by suppressing the postischemic activation of intrarenal myeloid cells.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
04 Faculty of Medicine > Institute of Anatomy
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:19 August 2009
Deposited On:10 Feb 2010 13:32
Last Modified:27 Nov 2013 17:37
Publisher:American Association of Immunologists
ISSN:0022-1767
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.4049/jimmunol.0900118
PubMed ID:19692646
Citations:Web of Science®. Times Cited: 40
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Scopus®. Citation Count: 41

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