Leukocyte urokinase plasminogen activator receptor and PSGL1 play a role in endogenous arterial fibrinolysis.
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.
Bai
Xufang
X
Henderson Research Centre and McMaster University, Hamilton, Ontario, Canada.
Weitz
Jeffrey I
JI
Gross
Peter L
PL
D015119:Aminocaproic Acid / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000293:injuries / Q000503:physiopathology; D001792:Blood Platelets / Q000473:pathology; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis / Q000235:genetics / Q000502:physiology*; D017708:Leukocyte Transfusion; D007962:Leukocytes / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood / Q000172:deficiency / Q000235:genetics
D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; C524899:Plaur protein, mouse; D055293:Receptors, Urokinase Plasminogen Activator; D005337:Fibrin; D014568:Urokinase-Type Plasminogen Activator; D015119:Aminocaproic Acid