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Thromb Haemost 2009; 102(06): 1212-1218
DOI: 10.1160/TH09-01-0038
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

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

Xufang Bai
1   Henderson Research Centre and McMaster University, Hamilton, Ontario, Canada
,
Jeffrey I. Weitz
1   Henderson Research Centre and McMaster University, Hamilton, Ontario, Canada
,
Peter L. Gross
1   Henderson Research Centre and McMaster University, Hamilton, Ontario, Canada
› Author AffiliationsFinancial support: This work was supported by the Canadian Institutes of Health Research (MOP-68908) with financial support for equipment from Hamilton Health Sciences. PLG is a recipient of the William E. Noonan Research Career Award from Hamilton Health Sciences. JIW holds a Canada Research Chair (Tier I) in Thrombosis and the HSFO/J.F. Mustard Chair in Cardiovascular Research at McMaster University.
Further Information

Publication History

Received: 16 January 2009

Accepted after major revision: 29 September 2009

Publication Date:
28 November 2017 (online)

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Summary

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.

Keywords

Thrombosis - mouse models - plasmin - tissue-type plasminogen activator - urokinase-type plasminogen activator receptor

 

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