Tissue-resident Macrophages Protect the Liver From Ischemia Reperfusion Injury via a Heme Oxygenase-1-Dependent Mechanism

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Tissue-resident Macrophages Protect the Liver From Ischemia Reperfusion Injury via a Heme Oxygenase-1-Dependent Mechanism. / Devey, L; Ferenbach, D; Mohr, Elodie; Sangster, K; Bellamy, CO; Hughes, J; Wigmore, SJ.

In: Molecular Therapy, Vol. 17, No. 1, 01.01.2009, p. 65-72.

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Devey, L ; Ferenbach, D ; Mohr, Elodie ; Sangster, K ; Bellamy, CO ; Hughes, J ; Wigmore, SJ. / Tissue-resident Macrophages Protect the Liver From Ischemia Reperfusion Injury via a Heme Oxygenase-1-Dependent Mechanism. In: Molecular Therapy. 2009 ; Vol. 17, No. 1. pp. 65-72.

Bibtex

@article{9596b7553c314c70a304367d7253d87d,
title = "Tissue-resident Macrophages Protect the Liver From Ischemia Reperfusion Injury via a Heme Oxygenase-1-Dependent Mechanism",
abstract = "Kupffer cells are the resident macrophage population of the liver and have previously been implicated in the pathogenesis of hepatic ischemia-reperfusion injury (IRI). Kupffer cells are the major site of expression of hepatic heme oxygenase-1 (HO-1), which has been shown to have anti-inflammatory actions and to protect animals and cells from oxidative injury. Kupffer cells and circulating monocytes were selectively ablated using liposomal clodronate (LC) in the CD11b DTR mouse before induction of hepatic ischemia. Kupffer cell depletion resulted in loss of HO-1 expression and increased susceptibility to hepatic IRI, whereas ablation of circulating monocytes did not affect IRI phenotype. Targeted deletion of HO-1 rendered mice highly susceptible to hepatic IRI. In vivo, HO-1 deletion resulted in pro-inflammatory Kupffer cell differentiation characterized by enhanced Ly6c and MARCO ( macrophage receptor with collagenous structure) expression as well as decreased F4/80 expression, mirrored by an expansion in immature circulating monocytes. In vitro, HO-1 inhibition throughout macrophage differentiation led to increased cell numbers, and pro-inflammatory Ly6c+ CD11c- F4/80- phenotype. These data support a critical role for tissue-resident macrophages in homeostasis following ischemic injury, and a co-dependence of HO-1 expression and tissue-resident macrophage differentiation.",
author = "L Devey and D Ferenbach and Elodie Mohr and K Sangster and CO Bellamy and J Hughes and SJ Wigmore",
year = "2009",
month = jan,
day = "1",
doi = "10.1038/mt.2008.237",
language = "English",
volume = "17",
pages = "65--72",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Tissue-resident Macrophages Protect the Liver From Ischemia Reperfusion Injury via a Heme Oxygenase-1-Dependent Mechanism

AU - Devey, L

AU - Ferenbach, D

AU - Mohr, Elodie

AU - Sangster, K

AU - Bellamy, CO

AU - Hughes, J

AU - Wigmore, SJ

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Kupffer cells are the resident macrophage population of the liver and have previously been implicated in the pathogenesis of hepatic ischemia-reperfusion injury (IRI). Kupffer cells are the major site of expression of hepatic heme oxygenase-1 (HO-1), which has been shown to have anti-inflammatory actions and to protect animals and cells from oxidative injury. Kupffer cells and circulating monocytes were selectively ablated using liposomal clodronate (LC) in the CD11b DTR mouse before induction of hepatic ischemia. Kupffer cell depletion resulted in loss of HO-1 expression and increased susceptibility to hepatic IRI, whereas ablation of circulating monocytes did not affect IRI phenotype. Targeted deletion of HO-1 rendered mice highly susceptible to hepatic IRI. In vivo, HO-1 deletion resulted in pro-inflammatory Kupffer cell differentiation characterized by enhanced Ly6c and MARCO ( macrophage receptor with collagenous structure) expression as well as decreased F4/80 expression, mirrored by an expansion in immature circulating monocytes. In vitro, HO-1 inhibition throughout macrophage differentiation led to increased cell numbers, and pro-inflammatory Ly6c+ CD11c- F4/80- phenotype. These data support a critical role for tissue-resident macrophages in homeostasis following ischemic injury, and a co-dependence of HO-1 expression and tissue-resident macrophage differentiation.

AB - Kupffer cells are the resident macrophage population of the liver and have previously been implicated in the pathogenesis of hepatic ischemia-reperfusion injury (IRI). Kupffer cells are the major site of expression of hepatic heme oxygenase-1 (HO-1), which has been shown to have anti-inflammatory actions and to protect animals and cells from oxidative injury. Kupffer cells and circulating monocytes were selectively ablated using liposomal clodronate (LC) in the CD11b DTR mouse before induction of hepatic ischemia. Kupffer cell depletion resulted in loss of HO-1 expression and increased susceptibility to hepatic IRI, whereas ablation of circulating monocytes did not affect IRI phenotype. Targeted deletion of HO-1 rendered mice highly susceptible to hepatic IRI. In vivo, HO-1 deletion resulted in pro-inflammatory Kupffer cell differentiation characterized by enhanced Ly6c and MARCO ( macrophage receptor with collagenous structure) expression as well as decreased F4/80 expression, mirrored by an expansion in immature circulating monocytes. In vitro, HO-1 inhibition throughout macrophage differentiation led to increased cell numbers, and pro-inflammatory Ly6c+ CD11c- F4/80- phenotype. These data support a critical role for tissue-resident macrophages in homeostasis following ischemic injury, and a co-dependence of HO-1 expression and tissue-resident macrophage differentiation.

U2 - 10.1038/mt.2008.237

DO - 10.1038/mt.2008.237

M3 - Article

C2 - 19002167

VL - 17

SP - 65

EP - 72

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 1

ER -