Summary
The mechanism of platelet-enhanced fibrinolysis is unclear. We therefore investigated
the fibrinolytic activity of human platelets and demonstrated that they contain a
tissue plasminogen activator (tPA)- like plasminogen activator, abbreviated as tPA-like-PA.
This activator was detected by ELISA in platelet incubation medium and in platelet
Triton extracts. Plasminogen activation assays showed that this tPA- like-PA could
induce plasminogen activation to form plasmin. Western blots of Triton extracts incubated
with anti-tPA antibody demonstrated a major 64-kD protein band, compared to a 70-kD
band for standard single chain tPA, plus a minor 118-kD band corresponding to a complex
of tPA-like-PA and plasminogen activator inhibitor (PAI-1). Western blots of Triton
extracts incubated with anti-PAI-1 antibody produced an approximately similar high-molecular-weight
(118 kD) protein band. Fibrin zymographic analysis of affinity-purified tPA-like-
PA demonstrated a major and a minor fibrin lysis zone, which approximately corresponded
to the tPA-like-PA and its complex with PAI-1 observed by Western blots. Immunogold
labelling and electron microscopy demonstrated that platelet activator, either as
the free form or co-localized with PAI-1, was present in granules and in channels
of the open canalicular system. We conclude that platelets contain a functionally
active tPA-like-PA, whose low fibrinolytic activity might be due to its readily forming
a complex with PAI-1. This functionally active tPA-like-PA might contribute to the
enhanced fibrinolytic activity of platelets observed in platelet-rich thrombi.
