MODULATION OF THE MACROPHAGE HEPATOCYTOTOXICITY AND PLASMINOGEN ACTIVATOR ACTIVITY OF ACTIVATED MACROPHAGES BY SERUM COMPONENTS FROM PATIENTS WITH LIVER DISEASES

Abstract

Activated macrophages exhibited cytotoxic effects on isolated liver cells and produced plasminogen activator in vitro. A high molecular weight fraction of normal human serum (Fr-1) was shown to reduce the macrophage-mediated hepatocytotoxicity and enhance the plasminogen activator activity of activated macrophages. Conversely, a lower molecular weight fraction of serum (Fr-3) was found to enhance the hepatotoxic potential and reduce the plasminogen activator activity of activated macrophages. Although similar effects were seen with serum fractions prepared from patients with acute hepatitis, somewhat different influences were observed with serum components from patients with chronic active hepatitis or liver cirrhosis: Fr-1 from patients with chronic active hepatitis was less active in reducing macrophage-mediated hepatocytotoxicity, and Fr-3 was more active in enhancing it, in comparison with corresponding fractions from individuals or patients with acute hepatitis. Fr-3 from patients with liver cirrhosis was shown to be remarkably less active in enhancing macrophage-mediated hepatocytotoxicity. Furthermore, Fr-1 from patients with liver cirrhosis reduced plasminogen activator activity, while Fr-3 was less active in reduing such activity.
These findings suggest that these serum components may regulate macrophage-mediated hepatocytotoxicity as well as plasminogen activator secretion of activated macrophages. Our studies also suggest the possibility that relative doses of these serum components may differ in various pathological conditions of the liver.