Cumberland P F, Pratten M K
Department of Anatomy, University of Leicester, UK.
Placenta. 1993 May-Jun;14(3):287-307. doi: 10.1016/s0143-4004(05)80428-x.
Previous work has shown that human serum supplemented with rat transferrin can support the normal growth of cultured rat conceptuses, but that supplementation with human transferrin has no such effect. Such results strongly suggest an hypothesis of species-specificity. This potential specificity was therefore investigated by comparing uptake, binding, competition and vectorial transport of both rat and human transferrin using two well-established systems, those of 17.5 day rat visceral yolk sacs and anembryonic yolk sacs in culture. The results of these investigations show that human transferrin displays a lower rate of uptake and lower binding affinity for the rat transferrin receptor than does rat transferrin. Human transferrin competes poorly with rat transferrin for receptor occupancy unless present in 20-fold excess. Both molecules are taken up by receptor-mediated endocytosis and are processed in a similar manner. Anembryonic yolk sac experiments show that a greater proportion of intact rat transferrin is transported to the exocoelomic fluid than is intact human transferrin. Binding analyses show a difference in binding affinities of the two molecules for the rat transferrin receptor and also that human transferrin exhibits negative cooperativity in its binding. This evidence strongly supports an hypothesis of species-specificity in the binding of transferrin to the transferrin receptor in the rat visceral yolk sac.
先前的研究表明,添加大鼠转铁蛋白的人血清能够支持培养的大鼠胚胎正常生长,但添加人转铁蛋白则无此效果。这些结果有力地支持了物种特异性假说。因此,利用两种成熟的系统,即培养的17.5天大的大鼠内脏卵黄囊和无胚胎卵黄囊,通过比较大鼠和人转铁蛋白的摄取、结合、竞争和向量运输,对这种潜在的特异性进行了研究。这些研究结果表明,与人转铁蛋白相比,人转铁蛋白对大鼠转铁蛋白受体的摄取率较低,结合亲和力也较低。除非人转铁蛋白的含量超过大鼠转铁蛋白20倍,否则其与大鼠转铁蛋白竞争受体占据的能力较差。两种分子均通过受体介导的内吞作用被摄取,并以类似的方式进行处理。无胚胎卵黄囊实验表明,完整的大鼠转铁蛋白被转运到胚外体腔液中的比例比完整的人转铁蛋白更高。结合分析表明,两种分子对大鼠转铁蛋白受体的结合亲和力存在差异,并且人转铁蛋白在结合过程中表现出负协同性。这一证据有力地支持了转铁蛋白与大鼠内脏卵黄囊中转铁蛋白受体结合存在物种特异性的假说。