Artigo
Paradoxical role of matrix metalloproteinases in liver injury and regeneration after sterile acute hepatic failure
Autor
Santos, Mônica Morais
Alvarenga, Débora Moreira
Mattos, Matheus Silvério
Lopes, Mateus Eustáquio
Marchesi, Sarah Cozzer
Araújo, Alan Moreira
Nakagaki, Brenda Naemi
David, Bruna Araújo
Souza, Viviane Aparecida De
Carvalho, Érika
Pereira, Rafaela Vaz Sousa
Marques, Pedro Elias
Mafra, Kassiana
Oliveira, Hortência Maciel de Castro
Miranda, Camila Dutra Moreira de
Diniz, Ariane Barros
Oliveira, Thiago Henrique Caldeira de
et al.
Institución
Resumen
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.