| Reduction of activated macrophages after ischaemia-reperfusion injury diminishes oxidative stress and ameliorates renal damage. | |
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MedLine Citation:
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PMID: 22402584 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Macrophages are major effectors of the local inflammatory response syndrome (LIRS) and influence the extent of ischaemia/reperfusion injury, thereby impacting organ function. Several subgroups of macrophages exist, representing distinct modes of action. The specific role of the subset expressing Fc gamma receptor (FcγR) 1 in the activated state of macrophages is poorly defined.METHODS: We induced a LIRS via 30 min of ischaemia in uninephrectomized rats, transgenic for the human FcγR1. Six hours after reperfusion, the treatment group was injected with a recombinant immunotoxin (IT) H22(scFv)-ETA' targeted against human FcγR1, which induced apoptosis of target cells. The placebo group received normal saline (NS). Contralateral kidneys served as healthy controls (Ctr). After 24 h of reperfusion, the animals were analysed.RESULTS: Targeted treatment with IT resulted in preserved renal function [NS versus IT treatment and baseline (creatinine: 69.2 ± 2.6, 54.7 ± 3.4 and 27.3 ± 1.0 μmol/L; P < 0.001)]. The number of all infiltrating monocytes were significantly reduced (CD68-positive cells per view field: NS 3.8 ± 0.4, IT 2.5 ± 0.2 and Ctr 1.2 ± 0.4; P < 0.05), renal histology improved and there was a reduced expression of renal fibronectin (NS 4.0 ± 0.4, IT 2.3 ± 0.2 and Ctr 1.1 ± 0.1; P < 0.001). Following IT administration, we also observed less expression of renal monocyte chemoattractant protein-1-positive cells per view field (NS 19.0 ± 1, IT 10.1 ± 0.8 and Ctr 2.0 ± 0.3; P < 0.001) as well as reduced systemic and local oxidative stress [serum malondialdehyde (MDA): NS 340 ± 30, IT 224 ± 36 versus baseline 140 ± 5 nmol/mL; P < 0.01]; renal MDA arbitrary units of fluorescence intensity: NS 3.7 ± 0.2, IT 1.8 ± 0.3 and Ctr 0.4 ± 0.2; P < 0.001.CONCLUSIONS: Reduction of FcγR1-up-regulated monocytic cells leads to preserved renal function and morphology in a rat model of ischaemia-triggered LIRS. Our results show that targeting activated macrophages is a valuable approach for ameliorating ischaemia-induced tissue injury. |
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Authors:
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Ngwi G Fet; Anette Fiebeler; Uwe Klinge; Joon-Keun Park; Stefan Barth; Theo Thepen; René H Tolba |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-8 |
Journal Detail:
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Title: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Volume: - ISSN: 1460-2385 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8706402 Medline TA: Nephrol Dial Transplant Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Department of Surgery, RWTH Aachen, Aachen, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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