Vampire bat salivary plasminogen activator is quiescent in human plasma in
the absence of fibrin unlike human tissue plasminogen activator
SJ Gardell, TR Hare, PW Bergum, GC Cuca, L O'Neill-Palladino and SM Zavodny
Department of Biological Chemistry, Merck Sharp & Dohme Research
Laboratories, West Point, PA 19486.
The vampire bat salivary plasminogen activator (Bat-PA) is a potent PA that
exhibits remarkable selectivity toward fibrin-bound plasminogen (Gardell et
al, J Biol Chem 256: 3568, 1989). Herein, we describe the activity of
recombinant DNA-derived Bat-PA (rBat-PA) in a human plasma milieu. rBat-PA
and recombinant human single-chain tissue plasminogen activator (rt-PA) are
similarly efficacious at lysing plasma clots. In stark contrast to rt-PA,
the addition of 250 nmol/L rBat-PA to plasma in the absence of a clot
failed to deplete plasminogen, alpha 2- antiplasmin and fibrinogen. The
lytic activities exhibited by finger- domain minus Bat-PA (F- rBat-PA) and
finger and epidermal growth factor- like domains minus Bat-PA (FG- rBat-PA)
were less than rBat-PA, especially at low concentrations of PA;
nevertheless, these truncated forms also possessed a strict requirement for
a fibrin cofactor. The loss of PA activity following the addition of
rBat-PA to plasma was slower than that observed when either rt-PA or
two-chain rt-PA was added. The efficacy, fibrin selectivity, and decreased
susceptibility to inactivation exhibited by rBat-PA in vitro in a human
plasma milieu suggests that rBat-PA may be superior to rt-PA for the
treatment of thrombotic complications.
Volume 76,
Issue 12,
pp. 2560-2564,
12/15/1990
Copyright © 1990 by The American Society of Hematology
