Cardier J, Romano E, Soyano A
Department of Experimental Medicine, Venezuelan Institute for Scientific Research (IVIC), Caracas, Venezuela.
Immunopharmacol Immunotoxicol. 1995 Nov;17(4):719-32. doi: 10.3109/08923979509037191.
Iron and ferritin impair a variety of immunological functions. To evaluate the effect of ferritin iron content on rat lymphocyte proliferative response, isoferritins that differ in their iron content and isoelectric point (pI) were isolated from iron overload rat livers by ultracentrifugation (isoferritins with high iron content and low pI) or crystallization (isoferritins with low iron content and high pI) methods. Additionally, commercial horse splenic ferritin (with a lower pI and higher iron content than rat isoferritins) was also tested. Proliferative response to Con A was decreased in a dose-dependent manner in all assays in which spleen cells were incubated with rat and horse isoferritins. However, isoferritins with higher iron contents (rat isoferritin obtained by ultracentrifugation and horse ferritin) caused a greater decrease of proliferative response at 5 and 25 micrograms/ml than the others. Rat and horse apoferritins showed no inhibitory effect on lymphocyte proliferative response, suggesting that the effect is due to iron probably through the damaging effect of reactive oxygen species generated by iron released by the isoferritins on lymphocyte functions. Additionally, the role of serum ferritin level on proliferative response was studied in an experimental model of iron overload in rats. An inverse relationship between the proliferative response and serum ferritin levels was observed. Our results suggest that the inhibitory effect of the isoferritins on lymphocyte proliferative response is due, at least partially, to the iron content of this protein and not exclusively to variation in pI as suggested by other authors. These results are in agreement with the possible immunosuppressor role of ferritin in vivo.
铁和铁蛋白会损害多种免疫功能。为了评估铁蛋白铁含量对大鼠淋巴细胞增殖反应的影响，通过超速离心法（高铁含量和低等电点（pI）的异铁蛋白）或结晶法（低铁含量和高等电点的异铁蛋白）从铁过载大鼠肝脏中分离出铁含量和等电点不同的异铁蛋白。此外，还测试了商业马脾铁蛋白（与大鼠异铁蛋白相比，pI较低且铁含量较高）。在所有将脾细胞与大鼠和马异铁蛋白一起孵育的试验中，对刀豆蛋白A的增殖反应均呈剂量依赖性降低。然而，高铁含量的异铁蛋白（通过超速离心获得的大鼠异铁蛋白和马铁蛋白）在5和25微克/毫升时比其他异铁蛋白导致增殖反应的降低幅度更大。大鼠和马脱铁铁蛋白对淋巴细胞增殖反应没有抑制作用，这表明该作用可能是由于铁，可能是通过异铁蛋白释放的铁产生的活性氧对淋巴细胞功能的损害作用。此外，在大鼠铁过载的实验模型中研究了血清铁蛋白水平对增殖反应的作用。观察到增殖反应与血清铁蛋白水平呈负相关。我们的结果表明，异铁蛋白对淋巴细胞增殖反应的抑制作用至少部分归因于该蛋白的铁含量，而并非如其他作者所暗示的仅归因于pI的变化。这些结果与铁蛋白在体内可能的免疫抑制作用一致。
