Qureshi G D, Guzelian P S, Vennart R M, Evans H J
Biochim Biophys Acta. 1985 Mar 21;844(3):288-95. doi: 10.1016/0167-4889(85)90129-6.
Because of the inherent difficulties of experimentation in intact animals, we used primary monolayer cultures of non-proliferating adult rat hepatocytes to study the effects of fibrinogen degradation products on fibrinogen biosynthesis. The freshly isolated hepatocytes obtained by collagenase perfusion of the liver in situ were cultured in a chemically defined serum-free medium. The rate of fibrinogen synthesis in control cultures was 40-50 pmol/2.5 X 10(6) cells per 24 h. Additions of 20, 60 or 100 micrograms of homologous stage I fibrinogen degradation products had no effect on fibrinogen synthesis. In contrast, addition of the same amounts of homologous or heterologous (human) stage III fibrinogen degradation products resulted in a concentration-dependent increase in fibrinogen biosynthesis without affecting the rate of synthesis of albumin. When purified stage III fibrinogen degradation products D and E (human) were tested in 10, 30 or 50 micrograms/3 ml medium only fragment E showed a significant increase in fibrinogen biosynthesis (1.9-, 2.8- and 5.6-fold, respectively, over the control cultures). The presence of excess fibrinogen had no effect. These results suggest that fibrinogen fragment E may be a specific stimulator of fibrinogen biosynthesis which may play an important role in maintaining normal levels of plasma fibrinogen.
由于在完整动物身上进行实验存在固有的困难，我们使用非增殖成年大鼠肝细胞的原代单层培养物来研究纤维蛋白原降解产物对纤维蛋白原生物合成的影响。通过原位肝脏胶原酶灌注获得的新鲜分离的肝细胞，在化学成分明确的无血清培养基中培养。对照培养物中纤维蛋白原的合成速率为每24小时40 - 50 pmol/2.5×10(6)个细胞。添加20、60或100微克同源I期纤维蛋白原降解产物对纤维蛋白原合成没有影响。相反，添加相同量的同源或异源（人）III期纤维蛋白原降解产物导致纤维蛋白原生物合成呈浓度依赖性增加，而不影响白蛋白的合成速率。当在10、30或50微克/3毫升培养基中测试纯化的III期纤维蛋白原降解产物D和E（人）时，只有片段E显示纤维蛋白原生物合成有显著增加（分别比对照培养物增加1.9倍、2.8倍和5.6倍）。过量纤维蛋白原的存在没有影响。这些结果表明，纤维蛋白原片段E可能是纤维蛋白原生物合成的特异性刺激物，可能在维持血浆纤维蛋白原的正常水平中起重要作用。
