Proteolytic enzymes released by liver macrophages may promote hepatic injury in a rat model of hepatic damage.

Using macrophages isolated from the livers of normal rats and from rats injected intravenously with Corynebacterium parvum 6 days previously, N-acetyl-glucosaminidase (NAG) and plasminogen activator (PA) production have been measured during in vitro culture. There was a significant increase (p less than 0.02) in the supernatant activity of NAG by the C. parvum recruited macrophages 8.05 +/- 1.17 nmol product/mg protein/h as compared with normal, 3.86 +/- 0.77 nmol product/mg protein/h. There was a similar increase in cellular NAG content by recruited macrophages 412 +/- 66 nmol product/mg protein compared with 153 +/- 35 nmol product/mg protein (p less than 0.01) in normals. When macrophages of either group were exposed in vitro to endotoxin alone or a combination of endotoxin followed by latex particles, NAG values were similar to those obtained from nonexposed cells. In contrast, PA supernatant production increased significantly (p less than 0.02) on exposure to endotoxin with a corresponding reduction in cellular PA content, but the cellular PA content and supernatant release were similar for each group of cells. There was a fourfold increase in the number of macrophages isolated from the C. parvum-treated livers/g liver weight. Thus, the hepatocytes in this model of liver injury are potentially exposed to a 10-fold increase in the concentration of the acid hydrolase NAG; potentiation of cell damage by the administration of endotoxin may be mediated through the observed increase in production of secretory enzymes such as plasminogen activator. In conclusion, this study supports the hypothesis that proteolytic products released by recruited and activated macrophages may result in hepatocyte damage.