Uptake of human recombinant tissue-type plasminogen activator by rat hepatocytes in vivo: An electron microscope autoradiographic study

The hepatic uptake of recombinant human tissue-type plasminogen activator (tPA) has been studied by electron microscope autoradiography (EMARG) of serial hepatic biopsies taken from anaesthetized, laparotomized rats following intravenous injection of 125 I labeled tPA. Serial blood samples showed both radiolabel and biologic activity to be eliminated from circulation with an initial half-life of approximately two minutes. Grain half-distance distribution profiles and grain density analysis showed that the para-sinusoidal region of the hepatic parenchymal cell is the only site in the liver to concentrate radiolabeled tPA after intravenous injection. These data support the hypothesis that the parenchymal cell is the principal cell responsible for hepatic clearance of tPA from circulation and suggest that receptor mediated endocytosis may be the mechanism of cellular uptake.