Figure 3.
Platelets can drive fibrinolysis via a plasmin-mediated mechanism. (A-B) Purified clots were formed from plasminogen-free fibrinogen (2.4 μM) and DL488 plasminogen-free fibrinogen (0.25 μM) in the presence or absence of glu-plasminogen (0.24 μM) and in the presence or absence of the indicated concentration of platelets. Clotting was initiated by thrombin (0.25 U/mL) and CaCl2 (5 mM), and clots were allowed to form for 30 minutes before addition of 75 nM tPA to the edge of the clots. Lysis was monitored by imaging every 15 minutes for 18 hours. (B) The distance lysed at 18 hours as a percentage of the plasminogen control (set to 100%). *P < .05 and **** P < .0001 compared with plasminogen control clots. (C-D) Purified clots were formed as above with or without 2.5 × 108 platelets/mL in the absence of DL488 fibrinogen. Turbidity was monitored every minute at 340 nm for 30 minutes at 37°C in a FLX-800 plate reader (Biotek Instruments). After 30-minute polymerization, 1 nM tPA (Genentech) was overlaid onto each clot, and turbidity was subsequently monitored every minute for 5 hours. (D) Fifty percent lysis times. ***P < .01 compared with no plasminogen control clots. Data are expressed as mean ± SEM, n ≥ 3.