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

L Devey, D Ferenbach, Elodie Mohr, K Sangster, CO Bellamy, J Hughes, SJ Wigmore

Research output: Contribution to journalArticle

110 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)65-72
Number of pages8
JournalMolecular Therapy
Issue number1
Publication statusPublished - 1 Jan 2009


Dive into the research topics of 'Tissue-resident Macrophages Protect the Liver From Ischemia Reperfusion Injury via a Heme Oxygenase-1-Dependent Mechanism'. Together they form a unique fingerprint.

Cite this