Fibrinogen biosynthesis

Haidaris, P. J. (1997). Induction of fibrinogen biosynthesis and secretion from cultured pulmonary epithelial cells. Blood 89, 873-882. 

Haidaris, P. J., Francis, G. W., Sporn, L. A., Arvan, D. S., Collichio, F. A., and Marder, V. J. (1989). Megakaryocyte and hepatocyte origins of human fibrinogen biosynthesis exhibit hepatocyte-specific expression of gamma chain-variant polypeptides. Blood 74, 743-750. 

Fibrinogen Biosynthesis by Isolated Liver. In our isolated rat liver perfusion studies homologous heparinized oxygenated rat blood is routinely diluted with Ringer s solution, so that its final volume is in-... 

Figure 12. Rate of fibrinogen biosynthesis in normal turnover in rat...

Under a variety of conditions it has not to date been possible to stimulate fibrinogen biosynthesis above this maximum value. Figure 12 outlines a calculation from which it is clear that the isolated perfused liver can synthesize fibrinogen at a rate three to four times that necessary to meet the needs of normal fibrinogen turnover, which we have found to occur with a half life of 1.5 days in the rat (30). 

Table I. Inhibition of Net Fibrinogen Biosynthesis by the Isolated Perfused Liver...

The antibiotic mitomycin C, introduced to give a concentration of 10 jLtg. per ml. in the perfusing blood at the outset, and a continuous infusion of a total of 1 mg. over the course of 4 to 5 hours, was also associated with significant suppression of fibrinogen biosynthesis. The concentrations of mitomycin C used here are at least ten times that which significantly inhibited cellular multiplication in isolated cell cultures. Further studies at lower concentration levels with both puromy-cin and mitomycin C are indicated. 

The view that this is true net biosynthesis of fibrinogen is supported by a variety of ancillary observations. Fibrinogen biosynthesis is suppressed in the presence of metabolic analogs, such as L-ethionine and puromycin, most markedly by the latter in spite of the maximal stimulus for production. Mitomycin C, which is believed to interfere with biosynthetic processes in the nucleus, also caused some suppression of fibrinogen biosynthesis. The isolated perfused liver in the presence of any of the three inhibitors used continues to function in an apparently normal manner in terms of bile secretion, linear urea production, amino acid oxidation, and glucose utilization. The effects of these inhibitors on the biosynthesis of the other plasma proteins will be described elsewhere. 

The exclusive role of the liver in the biosynthesis of fibrinogen, questioned by some, has been reaffirmed in isolated liver perfusion experiments in which maximal net biosynthesis of fibrinogen of 0.6 mg. per hour per gram wet weight of liver occurs. This approximates three to four times the normal rate of fibrinogen biosynthesis in turnover in the intact normal rat and occurs only in liver perfusions in which the stimulus of extreme hypofibrinogenemia associated with the use of completely defibrinated blood is present. 

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