Evidence for and characterization of a liver cell proliferation factor from blood plasma of partially hepatectomized rats.

A boiled extract acidified to pH 5.5 from the blood plasma of partially hepatectomized rats was treated with neuraminidase and injected i.p. into untreated rats. The DNA-synthesis of the liver cells showed a four-fold increase in comparison with controls. Extracts from the plasma of partially hepatectomized rats without neuraminidase treatment showed no increase in DNA-synthesis. Injections of boiled acid extracts from plasma of normal rats, however, showed no comparable differences before and after neuraminidase treatment. The activity of neuraminidase treated boiled, plasma extract is lost after treatment both with trypsin-chymotrypsin and with beta-galactosidase. Gel chrmoatography of the factor gave a molecular weight of about 38,000 D. The specific activity of the active extract after chromatography was raised by a factor of 300. According to affinity chromatography the factor was shown to be a glycoprotein containing N-Ac-glucosamine. The factor is inert with respect to the proliferation of spleen and kidney, i.e. it is organ specific. According to these results a regulatory system of hepatopoiesis is proposed.