Details

Autor(en) / Beteiligte

• Whyte, Claire S.
• Swieringa, Frauke
• Mastenbroek, Tom G.
• Lionikiene, Ausra S.
• Lancé, Marcus D.
• van der Meijden, PaolaE.J.
• Heemskerk, JohanW.M.
• Mutch, Nicola J.

Titel

Plasminogen associates with phosphatidylserine-exposing platelets and contributes to thrombus lysis under flow

Ist Teil von

• Blood, 2015-04, Vol.125 (16), p.2568-2578

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• The interaction of plasminogen with platelets and their localization during thrombus formation and fibrinolysis under flow are not defined. Using a novel model of whole blood thrombi, formed under flow, we examine dose-dependent fibrinolysis using fluorescence microscopy. Fibrinolysis was dependent upon flow and the balance between fibrin formation and plasminogen activation, with tissue plasminogen activator-mediated lysis being more efficient than urokinase plasminogen activator-mediated lysis. Fluorescently labeled plasminogen radiates from platelet aggregates at the base of thrombi, primarily in association with fibrin. Hirudin attenuates, but does not abolish plasminogen binding, denoting the importance of fibrin. Flow cytometry revealed that stimulation of platelets with thrombin/convulxin significantly increased the plasminogen signal associated with phosphatidylserine (PS)-exposing platelets. Binding was attenuated by tirofiban and Gly-Pro-Arg-Pro amide, confirming a role for fibrin in amplifying plasminogen binding to PS-exposing platelets. Confocal microscopy revealed direct binding of plasminogen and fibrinogen to different platelet subpopulations. Binding of plasminogen and fibrinogen co-localized with PAC-1 in the center of spread platelets. In contrast, PS-exposing platelets were PAC-1 negative, and bound plasminogen and fibrinogen in a protruding “cap.” These data show that different subpopulations of platelets harbor plasminogen by diverse mechanisms and provide an essential scaffold for the accumulation of fibrinolytic proteins that mediate fibrinolysis under flow. •Under physiological flow rates, plasminogen primarily accumulates on fibrin(ogen), emanating from platelets and initiates fibrinolysis.•Plasminogen is localized to defined “caps” on the surface of PS-exposing platelets in a fibrin(ogen)-dependent manner.