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

Yee, C; Main, NM; Terry, A; Stevanovski, I; Maczurek, A; Morgan, AJ; Calabro, S; Potter, AJ; Iemma, TL; Bowen, DG; Ahlenstiel, G; Warner, FJ; McCaughan, GW; McLennan, SV; Shackel, NA

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

Main, NM Terry, A Stevanovski, I Maczurek, A Morgan, AJ Calabro, S Potter, AJ Iemma, TL Bowen, DG Ahlenstiel, G Warner, FJ McCaughan, GW McLennan, SV Shackel, NA

Permalink

Publisher:: PUBLIC LIBRARY SCIENCE
Publication Type:: Journal Article
Citation:: PLoS One, 2019, 14, (7), pp. e0215557
Issue Date:: 2019

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download Published versionAdobe PDF (11.85 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Yee, C https://orcid.org/0000-0001-7243-5634
dc.contributor.author	Main, NM
dc.contributor.author	Terry, A
dc.contributor.author	Stevanovski, I
dc.contributor.author	Maczurek, A
dc.contributor.author	Morgan, AJ
dc.contributor.author	Calabro, S
dc.contributor.author	Potter, AJ
dc.contributor.author	Iemma, TL
dc.contributor.author	Bowen, DG
dc.contributor.author	Ahlenstiel, G
dc.contributor.author	Warner, FJ
dc.contributor.author	McCaughan, GW
dc.contributor.author	McLennan, SV
dc.contributor.author	Shackel, NA
dc.date.accessioned	2022-10-30T01:09:51Z
dc.date.available	2019-06-24
dc.date.available	2022-10-30T01:09:51Z
dc.date.issued	2019
dc.identifier.citation	PLoS One, 2019, 14, (7), pp. e0215557
dc.identifier.issn	1932-6203
dc.identifier.issn	1932-6203
dc.identifier.uri	http://hdl.handle.net/10453/162889
dc.description.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.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	PUBLIC LIBRARY SCIENCE
dc.relation.ispartof	PLoS One
dc.relation.isbasedon	10.1371/journal.pone.0215557
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	General Science & Technology
dc.subject.mesh	Animals
dc.subject.mesh	Basigin
dc.subject.mesh	Cell Aggregation
dc.subject.mesh	Hepatocytes
dc.subject.mesh	Humans
dc.subject.mesh	Leukocytes
dc.subject.mesh	Liver
dc.subject.mesh	Liver Cirrhosis
dc.subject.mesh	Liver Cirrhosis, Experimental
dc.subject.mesh	Male
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Up-Regulation
dc.subject.mesh	Liver
dc.subject.mesh	Leukocytes
dc.subject.mesh	Hepatocytes
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Liver Cirrhosis
dc.subject.mesh	Liver Cirrhosis, Experimental
dc.subject.mesh	Cell Aggregation
dc.subject.mesh	Up-Regulation
dc.subject.mesh	Male
dc.subject.mesh	Basigin
dc.title	CD147 mediates intrahepatic leukocyte aggregation and determines the extent of liver injury.
dc.type	Journal Article
utslib.citation.volume	14
utslib.location.activity	United States
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2022-10-30T01:09:42Z
pubs.issue	7
pubs.publication-status	Published online
pubs.volume	14
utslib.citation.issue	7

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/162889