Summary
Blood fibrinolytic activity is mediated by plasma and cellular components. We have
studied blood fibrinolytic activity in different species and investigated the distribution
pattern in rats after modulation with PAF, dexamethasone, or retinoic acid. Whole
blood and plasma activity were measured in an assay system using human or endogenous
fibrin as substrate. When human fibrin was used as substrate marked species differences
in distribution of fibrinolytic activity were observed. In rat and murine blood most
fibrinolytic activity was associated with the plasma fraction (70% and 50% respectively)
while in human and canine blood the plasma fraction contained only 30% of the blood
fibrinolytic activity. When endogenous fibrin was used as substrate the distribution
pattern of fibrinolytic activity in rat blood changed dramatically. Less than 25%
of the blood fibrinolytic activity was now present in the plasma fraction.
The fibrinolytic system was further investigated in rats using specific inhibitors
of proteolytic activity. Blood fibrinolytic activity could be inhibited for 33% by
antibodies raised against t-PA and 60% inhibition was obtained in the presence of
amiloride. No significant effect of elas-tinal (an inhibitor of elastase) could be
detected. Plasma fibrinolytic activity was not affected by these inhibitors. The fibrinolytic
activity in plasma could be enhanced about 100-fold after i. v. PAF administration
(10 μg/kg). This extra fibrinolytic activity could be fully blocked by antibodies
raised against t-PA. Oral administration of dexamethasone or retinoic acid affected
blood fibrinolytic activity by modulating selectively the activity mediated by the
cellular fraction. Dexamethasone treatment (1 mg/kg) resulted in a 59% decrease of
this fibrinolytic activity. Retinoic acid treatment (3 mg/kg) resulted in a 69% increase
of the fibrinolytic activity in this phase. Both compounds affected selectively the
t-PA activity.
We conclude that 1) the plasma as well as the cellular fraction contribute to the
blood fibrinolytic activity; 2) the plasma derived fibrinolytic activity as such is
a minor part of the total whole blood fibrinolytic activity (the mouse is an exception);
3) the rat blood fibrinolytic activity is evoked by u-PA (two third) and t-PA (one
third) mediated processes; 4) the blood fibrinolytic activity can be modulated, in
contrast to the plasma activity as such, by retinoic acid or dexamethasone; 5) the
plasma fibrinolytic activity is subject to modulation by compounds which evoke a direct
PA increase.
