Studies on the mechanism of liver injury by macrophage-mediated cytotoxicity--partial purification of cytotoxic factor detected in the culture supernatant of activated macrophages.

The culture supernatant of activated lymphocytes was shown to contain macrophage activating factor (MAF), a kind of lymphokine, which activated the peritoneal macrophages prepared from guinea pigs. When the culture fluid of the MAF-activated macrophages was added to the isolated liver cells, a significant inhibition of their albumin biosynthesis was demonstrated. The active material was recovered in a definitive fraction by gel filtration using a Sephadex G-75 column and this was further fractionated into two fractions by DEAE-cellulose column chromatography, suggesting that at least two kinds of active substances existed. By isoelectric focusing electrophoresis it was shown that these two active principles were substances having different isoelectric points, by isoelectric focusing electrophoresis. These results suggest that some cytotoxic or cytostatic materials are produced from the lymphokine-activated macrophages and they may participate in the occurrence of liver injury at least partially.