Vampire bat salivary plasminogen activator is quiescent in human plasma in the absence of fibrin unlike human tissue plasminogen activator.
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.
Gardell
S J
SJ
Department of Biological Chemistry, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Hare
T R
TR
Bergum
P W
PW
Cuca
G C
GC
O'Neill-Palladino
L
L
Zavodny
S M
SM
D000818:Animals; D002685:Chiroptera / Q000502:physiology*; D005337:Fibrin / Q000032:analysis / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D010949:Plasma / Q000737:chemistry / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D015849:Plasminogen Inactivators / Q000494:pharmacology; D012463:Saliva / Q000737:chemistry*; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000378:metabolism* / Q000502:physiology
D015849:Plasminogen Inactivators; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator