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

Thrombosis Research
P J BugelskiD G Morgan

Abstract

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 125I 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.

References

Feb 28, 1978·Biochemical and Biophysical Research Communications·P J Fraker, J C Speck
Dec 1, 1985·Journal of Leukocyte Biology·P J Bugelski
Dec 1, 1987·The Journal of Clinical Investigation·K A HajjarR L Nachman
Aug 15, 1985·Thrombosis Research·S NilssonC Mattsson
Apr 1, 1969·The Journal of Cell Biology·M M SalpeterE E Salpeter
Jan 1, 1984·Seminars in Thrombosis and Hemostasis·F Bachmann, I E Kruithof

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Citations

Dec 4, 1992·Annals of the New York Academy of Sciences·M OtterD C Rijken
Jan 1, 1990·Thrombosis Research. Supplement·D C RijkenT J van Berkel
May 23, 2012·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Thomas W Stief, Volker Klingmüller

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