Thrombospondin is a slow tight-binding inhibitor of plasmin.
Thrombospondin is a multifunctional glycoprotein of platelet alpha-granules and a variety of growing cells. We demonstrate that thrombospondin is a slow tight-binding inhibitor of plasmin as determined by loss of amidolytic activity, loss of ability to cleave fibrinogen, and decreased lysis zones in fibrin plate assays. Stoichiometric titrations indicate that approximately 1 mol of plasmin interacts with 1 mol of thrombospondin, an unexpected result considering the trimeric nature of thrombospondin. Plasmin in a complex with streptokinase or bound to epsilon-aminocaproic acid is protected from inhibition by thrombospondin, thereby implicating the lysine-binding kringle domains of plasmin in the inhibition process. Thrombospondin also inhibits urokinase plasminogen activator, but more slowly than plasmin, stimulates the amidolytic activity of tissue plasminogen activator, and has no effect on the amidolytic activity of alpha-thrombin or factor Xa. These results, therefore, identify thrombospondin as a new type of serine proteinase inhibitor and potentially important regulator of fibrinolysis.
Hogg
P J
PJ
Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden.
Stenflo
J
J
Mosher
D F
DF
D001792:Blood Platelets / Q000378:metabolism*; D005341:Fibrinolysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D013300:Streptokinase / Q000378:metabolism; D019699:Thrombospondins
D010980:Platelet Membrane Glycoproteins; D015842:Serine Proteinase Inhibitors; D019699:Thrombospondins; D013300:Streptokinase; D005341:Fibrinolysin