van Giezen J J, Chung-A-Hing J E, Vegter C B, Bouma B N, Jansen J W
Solvay Duphar B.V., Dept. of Biotechnology, Weesp, The Netherlands.
Thromb Haemost. 1994 Dec;72(6):887-92.
Blood fibrinolytic activity is mediated by plasma and cellular components. We have studied blood fibrinolytic activity in different species and investigated the distribution pattern in rats after modulation with PAF, dexamethasone, or retinoic acid. Whole blood and plasma activity were measured in an assay system using human or endogenous fibrin as substrate. When human fibrin was used as substrate marked species differences in distribution of fibrinolytic activity were observed. In rat and murine blood most fibrinolytic activity was associated with the plasma fraction (70% and 50% respectively) while in human and canine blood the plasma fraction contained only 30% of the blood fibrinolytic activity. When endogenous fibrin was used as substrate the distribution pattern of fibrinolytic activity in rat blood changed dramatically. Less than 25% of the blood fibrinolytic activity was now present in the plasma fraction. The fbrinolytic system was further investigated in rats using specific inhibitors of proteolytic activity. Blood fibrinolytic activity could be inhibited for 33% by antibodies raised against t-PA and 60% inhibition was obtained in the presence of amiloride. No significant effect of elastinal (an inhibitor of elastase) could be detected. Plasma fibrinolytic activity was not affected by these inhibitors. The fibrinolytic activity in plasma could be enhanced about 100-fold after i.v. PAF administration (10 micrograms/kg). This extra fibrinolytic activity could be fully blocked by antibodies raised against t-PA. Oral administration of dexamethasone or retinoic acid affected blood fibrinolytic activity by modulating selectively the activity mediated by the cellular fraction. Dexamethasone treatment (1 mg/kg) resulted in a 59% decrease of this fibrinolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
血液纤维蛋白溶解活性由血浆和细胞成分介导。我们研究了不同物种的血液纤维蛋白溶解活性，并研究了用血小板活化因子（PAF）、地塞米松或视黄酸调节后大鼠体内的分布模式。在以人纤维蛋白或内源性纤维蛋白为底物的检测系统中测量全血和血浆活性。当用人纤维蛋白作为底物时，观察到纤维蛋白溶解活性分布存在明显的物种差异。在大鼠和小鼠血液中，大部分纤维蛋白溶解活性与血浆部分相关（分别为70%和50%），而在人血和犬血中，血浆部分仅含有血液纤维蛋白溶解活性的30%。当以内源性纤维蛋白作为底物时，大鼠血液中纤维蛋白溶解活性的分布模式发生了显著变化。现在血浆部分中血液纤维蛋白溶解活性不到25%。使用蛋白水解活性的特异性抑制剂在大鼠中进一步研究了纤维蛋白溶解系统。抗组织型纤溶酶原激活物（t-PA）产生的抗体可抑制血液纤维蛋白溶解活性的33%，在存在氨氯吡咪的情况下可获得60%的抑制率。未检测到弹性蛋白酶抑制剂（弹性蛋白酶抑制剂）的显著作用。这些抑制剂对血浆纤维蛋白溶解活性没有影响。静脉注射PAF（10微克/千克）后，血浆纤维蛋白溶解活性可增强约100倍。这种额外的纤维蛋白溶解活性可被抗t-PA产生的抗体完全阻断。口服地塞米松或视黄酸通过选择性调节细胞部分介导的活性来影响血液纤维蛋白溶解活性。地塞米松治疗（1毫克/千克）导致这种纤维蛋白溶解活性降低59%。（摘要截断于250字）
