Henderson Research Centre and McMaster University, Hamilton, Ontario, Canada.
Thromb Haemost. 2009 Dec;102(6):1212-8. 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.
纤维蛋白是动脉血栓的重要组成部分。利用小鼠小动脉血栓形成模型，高速荧光显微镜显示，血栓中的纤维蛋白含量在数分钟内迅速增加，然后减少。纤维蛋白的减少与白细胞与血栓结合的过程相吻合，这个过程是由白细胞 P 选择素糖蛋白配体 1（PSGL-1）与激活血小板表面的 P 选择素相互作用介导的。由于白细胞具有尿激酶型纤溶酶原激活物（uPA）活性，我们使用缺乏 uPA 或 uPA 受体（uPAR）的小鼠来探索白细胞相关 uPA 对这些血栓中纤维蛋白丢失的贡献。与野生型对照相比，uPA 缺陷型小鼠和 uPAR 缺陷型小鼠的纤维蛋白丢失减少。将来自野生型小鼠的白细胞输注到 uPAR 缺陷型小鼠中，可将纤维蛋白丢失恢复到类似于野生型小鼠的水平。相比之下，输注缺乏 uPAR 或 PSGL-1 的小鼠的白细胞并不能增强纤维蛋白的丢失。因此，微动脉血栓中纤维蛋白的丢失至少部分是由白细胞相关的 uPA 介导的，该过程需要白细胞 uPAR 和 PSGL-1。
