Vampire bat salivary plasminogen activator promotes robust lysis of plasma clots in a plasma milieu without causing fluid phase plasminogen activation.
Vampire bat salivary plasminogen activator (BatPA), human tissue-type plasminogen activator (tPA) or streptokinase (SK) were incubated in human citrated plasma containing a plasma clot that was radiolabelled with iodine-125 fibrin(ogen). Complete clot dissolution by BatPA (30 nM) was associated with slight activation of "fluid phase" plasminogen; the plasma levels of functional fibrinogen and alpha 2-antiplasmin decreased by only 8 and 19%, respectively. Addition of SK (3,600 IU/ml) to the clot-containing plasma caused complete clot lysis and massive activation of the "fluid phase" plasminogen, leading to greater than 60 and 96% decreases of the functional levels of fibrinogen and alpha 2-antiplasmin, respectively. Incubation of tPA (30 nM) in clot-containing plasma caused complete clot lysis as well as substantial activation of "fluid phase" plasminogen; the plasma levels of functional fibrinogen and alpha 2-antiplasmin decreased by 45 and 79%, respectively. The profound degradation of fibrinogen in the SK and tPA but not BatPA-containing samples was confirmed by immunoblot analysis. Additional experiments showed that the presence of soluble clot lysate in plasma containing tPA enhanced the extent of fibrinogen degradation from 25% to greater than 60%; the addition of soluble clot lysate to the plasma containing BatPA did not prompt further fibrinogen degradation. Finally, studies using exogenous alpha 2-antiplasmin suggested that plasmin generated via tPA-mediated activation of "fluid phase" plasminogen does not play an important role in clot dissolution.
Hare
T R
TR
Department of Biological Chemistry, Merck Research Laboratories, West Point, PA 19486.
Gardell
S J
SJ
D000818:Animals; D002685:Chiroptera; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology; D013927:Thrombosis / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D000979:alpha-2-Antiplasmin / Q000494:pharmacology
D005338:Fibrin Fibrinogen Degradation Products; D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin; C069588:salivary plasminogen activator alpha 1, Desmodus rotundus; D005340:Fibrinogen; D010958:Plasminogen; D013300:Streptokinase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator