CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model.
Non-alcoholic fatty liver disease (NAFLD) is a common disease with a spectrum of presentations. The current study utilized a lithogenic diet model of NAFLD. The diet was fed to mice that are either resistant (AKR) or susceptible (BALB/c and C57BL/6) to hepatitis followed by molecular and flow cytome...
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doaj-2d952ef3ea704d31bb3f4661d3e421392020-11-25T01:51:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6524710.1371/journal.pone.0065247CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model.Charlotte E EganErin K DaugherityArlin B RogersDelbert S Abi AbdallahEric Y DenkersKirk J MaurerNon-alcoholic fatty liver disease (NAFLD) is a common disease with a spectrum of presentations. The current study utilized a lithogenic diet model of NAFLD. The diet was fed to mice that are either resistant (AKR) or susceptible (BALB/c and C57BL/6) to hepatitis followed by molecular and flow cytometric analysis. Following this, a similar approach was taken in congenic mice with specific mutations in immunological genes. The initial study identified a significant and profound increase in multiple ligands for the chemokine receptor CCR2 and an increase in CD44 expression in susceptible C57BL/6 (B6) but not resistant AKR mice. Ccr2(-/-) mice were completely protected from hepatitis and Cd44(-/-) mice were partially protected. Despite protection from inflammation, both strains displayed similar histological steatosis scores and significant increases in serum liver enzymes. CD45(+)CD44(+) cells bound to hyaluronic acid (HA) in diet fed B6 mice but not Cd44(-/-) or Ccr2(-/-) mice. Ccr2(-/-) mice displayed a diminished HA binding phenotype most notably in monocytes, and CD8(+) T-cells. In conclusion, this study demonstrates that absence of CCR2 completely and CD44 partially reduces hepatic leukocyte recruitment. These data also provide evidence that there are multiple redundant CCR2 ligands produced during hepatic lipid accumulation and describes the induction of a strong HA binding phenotype in response to LD feeding in some subsets of leukocytes from susceptible strains.http://europepmc.org/articles/PMC3676479?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Charlotte E Egan Erin K Daugherity Arlin B Rogers Delbert S Abi Abdallah Eric Y Denkers Kirk J Maurer |
spellingShingle |
Charlotte E Egan Erin K Daugherity Arlin B Rogers Delbert S Abi Abdallah Eric Y Denkers Kirk J Maurer CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model. PLoS ONE |
author_facet |
Charlotte E Egan Erin K Daugherity Arlin B Rogers Delbert S Abi Abdallah Eric Y Denkers Kirk J Maurer |
author_sort |
Charlotte E Egan |
title |
CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model. |
title_short |
CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model. |
title_full |
CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model. |
title_fullStr |
CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model. |
title_full_unstemmed |
CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model. |
title_sort |
ccr2 and cd44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Non-alcoholic fatty liver disease (NAFLD) is a common disease with a spectrum of presentations. The current study utilized a lithogenic diet model of NAFLD. The diet was fed to mice that are either resistant (AKR) or susceptible (BALB/c and C57BL/6) to hepatitis followed by molecular and flow cytometric analysis. Following this, a similar approach was taken in congenic mice with specific mutations in immunological genes. The initial study identified a significant and profound increase in multiple ligands for the chemokine receptor CCR2 and an increase in CD44 expression in susceptible C57BL/6 (B6) but not resistant AKR mice. Ccr2(-/-) mice were completely protected from hepatitis and Cd44(-/-) mice were partially protected. Despite protection from inflammation, both strains displayed similar histological steatosis scores and significant increases in serum liver enzymes. CD45(+)CD44(+) cells bound to hyaluronic acid (HA) in diet fed B6 mice but not Cd44(-/-) or Ccr2(-/-) mice. Ccr2(-/-) mice displayed a diminished HA binding phenotype most notably in monocytes, and CD8(+) T-cells. In conclusion, this study demonstrates that absence of CCR2 completely and CD44 partially reduces hepatic leukocyte recruitment. These data also provide evidence that there are multiple redundant CCR2 ligands produced during hepatic lipid accumulation and describes the induction of a strong HA binding phenotype in response to LD feeding in some subsets of leukocytes from susceptible strains. |
url |
http://europepmc.org/articles/PMC3676479?pdf=render |
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