Leukocyte urokinase plasminogen activator receptor and PSGL1 play a role in endogenous arterial fibrinolysis

• Published in: Thrombosis and haemostasis Vol. 102; no. 6; p. 1212
• Main Authors: Bai, Xufang, Weitz, Jeffrey I, Gross, Peter L
• Format: Journal Article
• Language: English
• Published: Germany 01.12.2009
• Subjects: Aminocaproic Acid - pharmacology; Animals; Arterioles - injuries; Arterioles - physiopathology; Blood Platelets - pathology; Disease Models, Animal; Fibrin - metabolism; Fibrinolysis - genetics; Fibrinolysis - physiology; Leukocyte Transfusion; Leukocytes - physiology; Membrane Glycoproteins - blood; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Urokinase Plasminogen Activator - blood; Receptors, Urokinase Plasminogen Activator - deficiency; Receptors, Urokinase Plasminogen Activator - genetics; Thrombosis - blood; Thrombosis - etiology; Thrombosis - physiopathology; Urokinase-Type Plasminogen Activator - blood; Urokinase-Type Plasminogen Activator - deficiency; Urokinase-Type Plasminogen Activator - genetics
• ISSN: 0340-6245
• DOI: 10.1160/TH09-01-0038

Fibrin is an integral component of arterial thrombi. Using a mouse model of arteriolar thrombosis, high-speed fluorescence microscopy reveals that, within minutes, the fibrin content of thrombi rapidly increases and then decreases. The decrease in fibrin coincides with leukocyte binding to the thrombi, a process mediated by the interaction of leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin on the surface of activated platelets. Because leukocytes possess urokinase-type plasminogen activator (uPA) activity, we used mice deficient in uPA or the uPA receptor (uPAR) to explore the contribution of leukocyte-associated uPA to the loss of fibrin from these thrombi. Fibrin loss in both uPA-deficient mice and uPAR-deficient mice was reduced compared with that in wild-type controls. Transfusion of leukocytes from wild-type mice into uPAR-deficient mice restored fibrin loss to levels similar to that in wild-type mice. In contrast, transfusion of leukocytes from mice deficient in uPAR or PSGL-1 did not enhance fibrin loss. Thus, fibrin loss from microarteriolar thrombi is mediated, at least in part, by leukocyte-associated uPA in a process that requires leukocyte uPAR and PSGL-1.