Fibrinolytic activity in blood is distributed over a cellular and the plasma fraction which can be modulated separately.
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 fbrinolytic 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 elastinal (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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
van Giezen
J J
JJ
Solvay Duphar B.V., Dept. of Biotechnology, Weesp, The Netherlands.
Chung-A-Hing
J E
JE
Vegter
C B
CB
Bouma
B N
BN
Jansen
J W
JW
D000818:Animals; D001772:Blood Cell Count; D001800:Blood Specimen Collection; D005591:Chemical Fractionation; D003907:Dexamethasone / Q000494:pharmacology*; D004285:Dogs; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors; D014212:Tretinoin / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D010972:Platelet Activating Factor; D014212:Tretinoin; D003907:Dexamethasone; D010196:Pancreatic Elastase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator