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Paradoxical Role of Matrix Metalloproteinases in Liver Injury and Regeneration after Sterile Acute Hepatic Failure.

Paradoxical Role of Matrix Metalloproteinases in Liver Injury and Regeneration after Sterile Acute Hepatic Failure.

Authors :
Alvarenga, Débora Moreira
Mattos, Matheus Silvério
Lopes, Mateus Eustáquio
Marchesi, Sarah Cozzer
Araújo, Alan Moreira
Nakagaki, Brenda Naemi
Santos, Mônica Morais
David, Bruna Araújo
De Souza, Viviane Aparecida
Carvalho, Érika
Sousa Pereira, Rafaela Vaz
Marques, Pedro Elias
Mafra, Kassiana
de Castro Oliveira, Hortência Maciel
de Miranda, Camila Dutra Moreira
Diniz, Ariane Barros
de Oliveira, Thiago Henrique Caldeira
Teixeira, Mauro Martins
Rezende, Rafael Machado
Antunes, Maísa Mota
Source :
Cells (2073-4409). Dec2018, Vol. 7 Issue 12, p247. 1p.
Publication Year :
2018

Abstract

Acetaminophen (APAP) poisoning is one of the leading causes of acute hepatic failure and liver transplantation is often the only lifesaving alternative. During the course of hepatocyte necrosis, an intense accumulation of neutrophils is often observed within the liver microenvironment. Despite the classic idea that neutrophil accumulation in tissues causes collateral tissue damage, there is a growing body of evidence showing that neutrophils can also orchestrate the resolution of inflammation. In this work, drug-induced liver injury was induced by oral administration of APAP and pharmacological intervention was made 12 h after this challenge. Liver injury and repair kinetics were evaluated by a novel combination of enzyme quantifications, ELISA, specific antagonists of neutrophil enzymes and confocal intravital microscopy. We have demonstrated that neutrophil infiltration is not only involved in injury amplification, but also in liver tissue repair after APAP-induced liver injury. In fact, while neutrophil depletion led to reduced hepatic necrosis during APAP poisoning, injury recovery was also delayed in neutropenic mice. The mechanisms underlying the neutrophil reparative role involved rapid degranulation and matrix metalloproteinases (MMPs) activity. Our data highlights the crucial role of neutrophils, in particular for MMPs, in the resolution phase of APAP-induced inflammatory response. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20734409
Volume :
7
Issue :
12
Database :
Academic Search Index
Journal :
Cells (2073-4409)
Publication Type :
Academic Journal
Accession number :
134075666
Full Text :
https://doi.org/10.3390/cells7120247