Cohen S, Vernier R L, Michael A F
Am J Pathol. 1983 Feb;110(2):170-81.
The effect of charge on the tissue distribution of ferritin was evaluated in rats following intravenous administration of 3 monomeric species preparatively separated by molecular sieve chromatography from aggregated ferritin and having the same molecular weight but differing only in electrostatic charge: native ferritin, with a isoelectric point (pI) of 4.5 (NF); cationized ferritin, with a pI of 6.4-7.4 (CF 7.0); and cationized ferritin, with a pI of 8.25-8.75 (CF 8.5). At varying time intervals (30 minutes to 72 hours) after the administration of these ferritins in a dose of 10 mg/100 g, the levels in the blood were determined, the tissue (kidney, liver, spleen) distribution semiquantitatively evaluated by immunofluorescence (IF), and electron microscopic examination (EM) of the kidney carried out. The following results were obtained: 1) The plasma levels of CF (8.5) and CF (7.0) were significantly higher than NF after 6 hours. NF was not detected after 24 hours, whereas CF continued to circulate at 72 hours. 2) There was a striking decrease in the uptake of CF (7.0) and CF (8.5), when compared with NF, by Kupffer cells and splenic phagocytes in the red pulp at all time periods. 3) In the glomerulus, NF was found primarily in the mesangium and gradually disappeared over a period of 72 hours, whereas CF was present in greater amounts and persisted for longer periods of time in the mesangium and in the peripheral capillary wall. By electron microscopy, CF (8.5) could be seen in th lamina rara and within the mesangium in small aggregates aligned parallel to mesangial cell processes, whereas NF and CF (7.0) were distributed homogeneously throughout the mesangial matrix. 4) NF, but not CF, was also observed surrounding blood vessels and in interstitial phagocytes. These in vivo studies demonstrate that the electrostatic charge of ferritin affects its uptake in vivo by components of the mononuclear phagocytic system (MPS). The persistence and distribution of CF in glomeruli is a consequence of higher blood levels associated with impaired phagocytic uptake as well as charge-related binding to sites within the glomeruli.
通过静脉注射从聚合铁蛋白中经分子筛色谱法制备分离得到的3种单体物质，评估电荷对铁蛋白组织分布的影响。这3种单体物质分子量相同，但仅静电电荷不同：天然铁蛋白，其等电点（pI）为4.5（NF）；阳离子化铁蛋白，pI为6.4 - 7.4（CF 7.0）；阳离子化铁蛋白，pI为8.25 - 8.75（CF 8.5）。以10 mg/100 g的剂量给予这些铁蛋白后，在不同时间间隔（30分钟至72小时）测定血液中的水平，通过免疫荧光（IF）半定量评估组织（肾脏、肝脏、脾脏）分布，并对肾脏进行电子显微镜检查（EM）。得到以下结果：1）6小时后，CF（8.5）和CF（7.0）的血浆水平显著高于NF。24小时后未检测到NF，而CF在72小时时仍在循环。2）在所有时间段，与NF相比，CF（7.0）和CF（8.5）被库普弗细胞和红髓中的脾吞噬细胞摄取的量显著减少。3）在肾小球中，NF主要存在于系膜中，并在72小时内逐渐消失，而CF在系膜和外周毛细血管壁中的含量更高且持续时间更长。通过电子显微镜观察，CF（8.5）可见于肾小球基底膜的内疏松层以及系膜中，呈与系膜细胞突起平行排列的小聚集体，而NF和CF（7.0）均匀分布于整个系膜基质中。4）在血管周围和间质吞噬细胞中也观察到了NF，但未观察到CF。这些体内研究表明，铁蛋白的静电电荷影响其在体内被单核吞噬细胞系统（MPS）成分的摄取。CF在肾小球中的持续存在和分布是由于与吞噬摄取受损相关的较高血液水平以及与肾小球内位点的电荷相关结合所致。
