FARQUHAR M G, PALADE G E
J Biophys Biochem Cytol. 1960 Apr;7(2):297-304. doi: 10.1083/jcb.7.2.297.
Ferritin was used as a tracer to study the mechanism by which proteins are segregated into droplets by the visceral epithelium of glomerular capillaries. In glomeruli from both normal and aminonucleoside-nephrotic rats ferritin molecules introduced into the general circulation penetrated the endothelial openings and were seen at various levels in the basement membrane. Striking differences between nephrotic and controls were seen only in the amount of ferritin incorporated into the epithelium. In normal animals, a few ferritin molecules were seen in small invaginations of the cell membrane limiting the foot processes, within minute vesicles in the epithelium, or within occasional large vacuoles and dense bodies. In nephrotics, epithelial pinocytosis was marked, and numerous ferritin molecules were seen within membrane invaginations and in small cytoplasmic vesicles at all time points. After longer intervals, the concentration of ferritin increased in vacuoles and particularly within the dense bodies or within structures with a morphology intermediate between that of vacuoles and dense bodies. In nephrotic animals cleft-like cavities or sinuses were frequently encountered along the epithelial cell surface facing the urinary spaces. Some of these sinuses contained material resembling that filling the dense bodies except that it appeared less compact. The findings suggest that ferritin molecules-and presumably other proteins which penetrate the basement membrane-are picked up by the epithelium in pinocytotic vesicles and transported via the small vesicles to larger vacuoles which are subsequently transformed into dense bodies by progressive condensation. The content of the dense bodies may then undergo partial digestion and be extruded into the urinary spaces where it disperses. The activity of the glomerular epithelium in the incorporation and segregation of protein is similar in normal and nephrotic animals, except that the rate is considerably higher in nephrosis where the permeability of the glomerular basement membrane is greatly increased.
铁蛋白被用作示踪剂，以研究蛋白质被肾小球毛细血管内脏上皮细胞分隔成液滴的机制。在正常大鼠和氨基核苷肾病大鼠的肾小球中，引入体循环的铁蛋白分子穿过内皮孔，并在基底膜的不同层面可见。肾病组和对照组之间的显著差异仅见于上皮细胞摄取的铁蛋白量。在正常动物中，在限制足突的细胞膜小凹陷处、上皮细胞内的微小囊泡中或偶尔出现的大液泡和致密小体中可见少量铁蛋白分子。在肾病大鼠中，上皮细胞的胞饮作用明显，在所有时间点，在膜凹陷和小细胞质囊泡内可见大量铁蛋白分子。较长时间后，液泡中铁蛋白浓度增加，特别是在致密小体或形态介于液泡和致密小体之间的结构内。在肾病动物中，沿面向尿腔的上皮细胞表面经常出现裂隙样腔隙或窦。其中一些窦所含物质类似于填充致密小体的物质，只是看起来没那么致密。这些发现表明，铁蛋白分子以及可能穿透基底膜的其他蛋白质，被上皮细胞通过胞饮小泡摄取，并通过小囊泡运输到较大的液泡，随后通过渐进性浓缩转化为致密小体。致密小体的内容物随后可能经历部分消化，并被挤出到尿腔中并在其中分散。正常动物和肾病动物中肾小球上皮细胞在蛋白质摄取和分隔方面的活性相似，只是在肾病时，肾小球基底膜通透性大大增加，其速率要高得多。
