CD147 mediates intrahepatic leukocyte aggregation and determines the extent of liver injury

CD147 mediates intrahepatic leukocyte aggregation and determines the extent of liver injury.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1371/journal.pone.0215557
Journal or Publication Title: PLOS ONE
Volume: 14
Number: 7
Page Range: e0215557
Date: 2019
Divisions: Liver Immunology
Liver Injury and Cancer
Depositing User: General Admin
Identification Number: 10.1371/journal.pone.0215557
ISSN: 1932-6203
Date Deposited: 21 Dec 2020 23:02
Abstract:

Background: Chronic inflammation is the driver of liver injury and results in progressive fibrosis and eventual cirrhosis with consequences including both liver failure and liver cancer. We have previously described increased expression of the highly multifunctional glycoprotein CD147 in liver injury. This work describes a novel role of CD147 in liver inflammation and the importance of leukocyte aggregates in determining the extent of liver injury.

Methods: Non-diseased, progressive injury, and cirrhotic liver from humans and mice were examined using a mAb targeting CD147. Inflammatory cell subsets were assessed by multiparameter flow cytometry.

Results: In liver injury, we observe abundant, intrahepatic leukocyte clusters defined as ≥5 adjacent CD45+ cells which we have termed "leukocyte aggregates". We have shown that these leukocyte aggregates have a significant effect in determining the extent of liver injury. If CD147 is blocked in vivo, these leukocyte aggregates diminish in size and number, together with a marked significant reduction in liver injury including fibrosis. This is accompanied by no change in overall intrahepatic leukocyte numbers. Further, blocking of aggregation formation occurs prior to an appreciable increase in inflammatory markers or fibrosis. Additionally, there were no observed, "off-target" or unpredicted effects in targeting CD147.

Conclusion: CD147 mediates leukocyte aggregation which is associated with the development of liver injury. This is not a secondary effect, but a cause of injury as aggregate formation proceeds other markers of injury. Leukocyte aggregation has been previously described in inflammation dating back over many decades. Here we demonstrate that leukocyte aggregates determine the extent of liver injury.

Creators:
Creators
Email
Mukhopadhyay, Partha
UNSPECIFIED
Yee, Christine
UNSPECIFIED
Main, Nathan M.
UNSPECIFIED
Terry, Alexandra
UNSPECIFIED
Stevanovski, Igor
UNSPECIFIED
Maczurek, Annette
UNSPECIFIED
Morgan, Alison J.
UNSPECIFIED
Calabro, Sarah
UNSPECIFIED
Potter, Alison J.
UNSPECIFIED
Iemma, Tina L.
UNSPECIFIED
Bowen, David G.
UNSPECIFIED
Ahlenstiel, Golo
UNSPECIFIED
Warner, Fiona J.
UNSPECIFIED
McCaughan, Geoffrey W.
UNSPECIFIED
McLennan, Susan V.
UNSPECIFIED
Shackel, Nicholas A.
UNSPECIFIED
Last Modified: 21 Dec 2020 23:02
URI: https://eprints.centenary.org.au/id/eprint/187

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