Summary
Three murine monoclonal antibodies to tissue-type plasminogen activator (t-PA) were
evaluated for their effects on the binding of iodinated t-PA to cultured human hepatoma
cells (Hep G2), and on extending the half-life of t-PA injected into rabbits. Two
of the antibodies, AE5 and EG2, significantly inhibited t-PA binding in vitro, and
extended the in vivo half-life of t-PA four to five-fold. A third antibody, BA10,
which had a much smaller inhibitory effect on t-PA binding, had no influence in extending
t-PA’s half-life. MOPC-21, a control antibody not directed to t-PA, had no effect
on either test. Our results are the first to correlate different compounds’ effects
on t-PA binding with their ability to retard t-PA clearance in vivo, and provide additional
evidence for the importance of a liver cell receptor in the t-PA clearance process.
Keywords
Tissue-type plasminogen activator - Hep G2 human hepatoma cells