再生肝ラットにおける脾臓および胸腺由来リンパ細胞による肝損傷シグナル受容にもとづく肝細胞増殖因子の血清内誘導 : 当研究室における最近5年間の研究のまとめ(Bucher's Theoryへの提言)

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Spleen lymphocytes were isolated from 10-week old, male Sprague-Dawley rats, and cultivated in an RPMI-1640 medium containing 3% serum obtained from the portal vein of Sprague-Dawley rats on which 70% partial hepatectomy had been performed. The spleen lymphocytes increased in number when cultivated in a medium supplemented with portal vein serum obtained 4 to 48 hours after operation. In addition, the DNA level was raised and glucose consumption accelerated. However, sera obtained from normal rats or rats on which a sham operation had been performed, showed no such activities. Next, spleen lymphocytes obtained from Sprague-Dawley rats that were capable of forming antibodies against sheep red blood corpuscle (SRBC), were cultivated in a medium to which had been added portal vein serum of rats that had suffered from hepatitis, cirrhosis or hepatoma induced by the administration of carcinogens for 110-170 days, such as O-aminoazotoluene and 3'-methyl-4-dimethylaminoazobenzene. In this experiment, the lymphocyte level showed no changes. On the other hand, these spleen lymphocytes underwent active proliferation when cultivated in a medium to which rat protal vein serum obtained 24 hours after 70% partial hepatectomy had been added, and a large number of plaque forming cells were produced. Subsequently, isolation of the spleen and the thymus lymphocytes was carried out 4, 8, 12, and 24 hours after 70% partial hepatectomy, and these cells were injected, after having been washed, into the vein in the tail of normal rats. Tewnty-four hours after the injection, portal vein serum was collected from each rat, and added to the WE medium in a concentration of 5%. Hepatocytes isolated from normal rats by means of collagenase perfusion were then cultivated in these media at 37℃ under an atmosphere of 5% CO_2-95% air. In each medium, proliferation of the hepatocytes and increase in the amounts of DNA and cell proteins were observed. However, there were no such activities in portal vein sera obtained from rats injected in the tail vein with spleen or thymus lymphocytes of normal rats. Furthermore, an increase both in the amount of cell proteins and in the number of hepatocytes were observed when hepatocytes isolated from normal rats were cultivated in a medium supplemented with portal vein serum which had been obtained 4 hours after injection of thyms lymphocytes into the tail vein of normal rats; the thymus lymphocytes used in this experiment were isolated from normal rats, incubated at 37℃ under an atmosphere of 5% CO_2-95% air in portal vein serum obtained 24 hours after 70% partial hepatectomy, and washed before use. These results suggest that, in the process in which the damaged liver progresses toward normal regeneration instead to toward canceration, the spleen and thymus lymphocytes play a certain role, and that the receptors of these lymphocytes in the body fluids receive signals which indicate liver damage and transfer these signals to the mechanism by which the growth factor of the hepatocytes for the regeneration of the liver are induced in serum.
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高橋直躬
明治大学農

再生肝ラットにおける脾臓および胸腺由来リンパ細胞による肝損傷シグナル受容にもとづく肝細胞増殖因子の血清内誘導 : 当研究室における最近5年間の研究のまとめ(Bucher's Theoryへの提言)

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