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

Autor: Yee C; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia.; Gastroenterology and Liver Laboratory, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia., Main NM; Gastroenterology and Liver Laboratory, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia., Terry A; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia.; Gastroenterology and Liver Laboratory, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia., Stevanovski I; Gastroenterology and Liver Laboratory, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia., Maczurek A; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia., Morgan AJ; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia., Calabro S; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia., Potter AJ; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia., Iemma TL; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia., Bowen DG; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia.; A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia., Ahlenstiel G; Western Sydney School of Medicine, Blacktown Hospital, Blacktown, NSW, Australia., Warner FJ; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia., McCaughan GW; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia.; A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia., McLennan SV; Department of Endocrinology, Department of Medicine and Bosch Institute, Royal Prince Alfred Hospital, The University of Sydney, NSW, Australia., Shackel NA; Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, NSW, Australia.; Gastroenterology and Liver Laboratory, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia.; A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.; Liverpool Hospital, Liverpool, NSW, Australia.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2019 Jul 10; Vol. 14 (7), pp. e0215557. Date of Electronic Publication: 2019 Jul 10 (Print Publication: 2019).
DOI: 10.1371/journal.pone.0215557
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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