Battelli M G, Buonamici L, Bolognesi A, Stirpe F
Dipartimento di Patologia Sperimentale, Università di Bologna, Italy.
Hepatology. 1994 Oct;20(4 Pt 1):940-7. doi: 10.1002/hep.1840200424.
A Ber-H2/saporin immunotoxin, consisting of the single-chain ribosome-inactivating protein saporin-S6 and the anti-CD30 monoclonal antibody Ber-H2, gave encouraging results in the treatment of refractory Hodgkin's disease but caused a transient hepatotoxicity. The accumulation of Ber-H2/saporin conjugate and of its components by rat liver parenchymal and nonparenchymal cells was studied. The in vivo concentration of intravenously injected Ber-H2/saporin, saporin or Ber-H2 in nonparenchymal cells was 4-, 25- and 11-fold higher, respectively, than that in parenchymal cells. Adherent in vitro cultured nonparenchymal cells, mostly Kupffer cells, accumulated the proteins approximately 10 times more than parenchymal cells; traces of free saporin were taken up by both types of cells. In vitro protein synthesis by both cell types was inhibited by 50% at nanomolar concentrations of saporin. Nonparenchymal cells were sensitive to Ber-H2/saporin at picomolar concentrations, whereas parenchymal cells were unaffected by the immunotoxin up to 100 pmol/L. The results of the uptake of, and the sensitivity to, the immunotoxin suggest that the sensitivity of liver cells is proportional to the uptake and that the in vivo damage to parenchymal cells is at least in part mediated by the toxicity to nonparenchymal liver cells.
一种由单链核糖体失活蛋白皂草素 - S6和抗CD30单克隆抗体Ber - H2组成的Ber - H2/皂草素免疫毒素，在难治性霍奇金病的治疗中取得了令人鼓舞的结果，但引起了短暂的肝毒性。研究了大鼠肝实质细胞和非实质细胞对Ber - H2/皂草素偶联物及其组分的摄取情况。静脉注射的Ber - H2/皂草素、皂草素或Ber - H2在非实质细胞中的体内浓度分别比实质细胞高4倍、25倍和11倍。体外培养的贴壁非实质细胞（主要是库普弗细胞）积累蛋白质的量大约是实质细胞的10倍；两种细胞类型都摄取了微量的游离皂草素。在纳摩尔浓度的皂草素作用下，两种细胞类型的体外蛋白质合成均被抑制50%。非实质细胞在皮摩尔浓度下对Ber - H2/皂草素敏感，而实质细胞在高达100 pmol/L的免疫毒素作用下不受影响。免疫毒素摄取和敏感性的结果表明，肝细胞的敏感性与摄取量成正比，并且体内对实质细胞的损伤至少部分是由对肝非实质细胞的毒性介导的。
