Role of plasminogen in macrophage accumulation during liver repair

Abstract 

Introduction

Although the involvement of plasminogen in liver repair has been reported, its roles are still poorly understood. Here, we investigated the role of plasminogen in accumulations of macrophages and neutrophils after liver injury in mice with gene deficient of plasminogen (Plg^−/−) or its wild type (Plg^+/+).

Materials and Methods

Mice received traumatic liver injury caused by stabbing on the lobe or hepatic ischemia-reperfusion, and the damaged sites were histologically analyzed.

Results

After the traumatic liver injury, both the stab wound and the damaged tissue were decreased until day 7 in the Plg^+/+ mice. In contrast, both the stab wound and the damaged tissue were still remained until day 7 in the Plg^−/− mice. On day 4 after traumatic liver injury, macrophages were abundant at the surrounding area of the damaged site in the Plg^+/+ mice. However, the macrophage accumulation was impaired in the Plg^−/− mice. After hepatic ischemia-reperfusion injury, macrophage accumulation and decrease in the damaged tissue were also observed in the Plg^+/+ mice until day 7. In contrast, these responses were also impaired in the Plg^−/− mice. Furthermore, neutrophil accumulation at the surrounding area of the damaged site was also impaired in the Plg^−/− mice on day 4 after both liver traumatic liver injury and hepatic ischemia-reperfusion injury.

Conclusions

Our data indicate that plasminogen plays a crucial role in macrophage accumulation together with the neutrophil accumulation after liver injury in both models, which may be essential for triggering the subsequent healing responses including decrease in the damaged tissue.

Abbreviations: ECM, extracellular matrix, PA, plasminogen activator, MMP, matrix metalloproteinase, Plg, plasminogen, Plg^−/−, plasminogen gene deficient, Plg^+/+, wild-type mice for Plg^−/− mice, H&E, hematoxylin-eosin, MCP-1, monocyte chemoattractant protein-1

Keywords: Plasminogen, Macrophage accumulation, Traumatic liver injury, Hepatic ischemia-reperfusion injury, Liver repair