Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration

Liver progenitor cells (LPCs) are necessary for repair in chronic liver disease because the remaining hepatocytes cannot replicate. However, LPC numbers also correlate with disease severity and hepatocellular carcinoma risk. Thus, the progenitor cell response in diseased liver may be regulated to op...

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Main Authors: Elsegood, Caryn, Chan, C., Degli-Esposti, M., Wikstrom, M., Domenichini, A., Lazarus, K., van Rooijen, N., Ganss, R., Olynyk, John, Yeoh, G.
Format: Journal Article
Published: John Wiley and Sons Inc. 2015
Online Access:http://hdl.handle.net/20.500.11937/23478
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author Elsegood, Caryn
Chan, C.
Degli-Esposti, M.
Wikstrom, M.
Domenichini, A.
Lazarus, K.
van Rooijen, N.
Ganss, R.
Olynyk, John
Yeoh, G.
author_facet Elsegood, Caryn
Chan, C.
Degli-Esposti, M.
Wikstrom, M.
Domenichini, A.
Lazarus, K.
van Rooijen, N.
Ganss, R.
Olynyk, John
Yeoh, G.
author_sort Elsegood, Caryn
building Curtin Institutional Repository
collection Online Access
description Liver progenitor cells (LPCs) are necessary for repair in chronic liver disease because the remaining hepatocytes cannot replicate. However, LPC numbers also correlate with disease severity and hepatocellular carcinoma risk. Thus, the progenitor cell response in diseased liver may be regulated to optimize liver regeneration and minimize the likelihood of tumorigenesis. How this is achieved is currently unknown. Human and mouse diseased liver contain two subpopulations of macrophages with different ontogenetic origins: prenatal yolk sac-derived Kupffer cells and peripheral blood monocyte-derived macrophages. We examined the individual role(s) of Kupffer cells and monocyte-derived macrophages in the induction of LPC proliferation using clodronate liposome deletion of Kupffer cells and adoptive transfer of monocytes, respectively, in the choline-deficient, ethionine-supplemented diet model of liver injury and regeneration. Clodronate liposome treatment reduced initial liver monocyte numbers together with the induction of injury and LPC proliferation. Adoptive transfer of monocytes increased the induction of liver injury, LPC proliferation, and tumor necrosis factor-a production. Conclusion: Kupffer cells control the initial accumulation of monocyte-derived macrophages. These infiltrating monocytes are in turn responsible for the induction of liver injury, the increase in tumor necrosis factor-a, and the subsequent proliferation of LPCs.
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spelling curtin-20.500.11937-234782019-02-19T05:35:05Z Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration Elsegood, Caryn Chan, C. Degli-Esposti, M. Wikstrom, M. Domenichini, A. Lazarus, K. van Rooijen, N. Ganss, R. Olynyk, John Yeoh, G. Liver progenitor cells (LPCs) are necessary for repair in chronic liver disease because the remaining hepatocytes cannot replicate. However, LPC numbers also correlate with disease severity and hepatocellular carcinoma risk. Thus, the progenitor cell response in diseased liver may be regulated to optimize liver regeneration and minimize the likelihood of tumorigenesis. How this is achieved is currently unknown. Human and mouse diseased liver contain two subpopulations of macrophages with different ontogenetic origins: prenatal yolk sac-derived Kupffer cells and peripheral blood monocyte-derived macrophages. We examined the individual role(s) of Kupffer cells and monocyte-derived macrophages in the induction of LPC proliferation using clodronate liposome deletion of Kupffer cells and adoptive transfer of monocytes, respectively, in the choline-deficient, ethionine-supplemented diet model of liver injury and regeneration. Clodronate liposome treatment reduced initial liver monocyte numbers together with the induction of injury and LPC proliferation. Adoptive transfer of monocytes increased the induction of liver injury, LPC proliferation, and tumor necrosis factor-a production. Conclusion: Kupffer cells control the initial accumulation of monocyte-derived macrophages. These infiltrating monocytes are in turn responsible for the induction of liver injury, the increase in tumor necrosis factor-a, and the subsequent proliferation of LPCs. 2015 Journal Article http://hdl.handle.net/20.500.11937/23478 10.1002/hep.27977 John Wiley and Sons Inc. fulltext
spellingShingle Elsegood, Caryn
Chan, C.
Degli-Esposti, M.
Wikstrom, M.
Domenichini, A.
Lazarus, K.
van Rooijen, N.
Ganss, R.
Olynyk, John
Yeoh, G.
Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration
title Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration
title_full Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration
title_fullStr Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration
title_full_unstemmed Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration
title_short Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration
title_sort kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration
url http://hdl.handle.net/20.500.11937/23478