Miura K, Takahashi Y, Shirasawa H
Lab Invest. 1985 Oct;53(4):453-63.
Localization of serum amyloid A protein (SAA) was observed by direct peroxidase-labeled antibody method. SAA was induced in mice by a single subcutaneous injection of casein. Before injection, trace amounts of SAA were detected in a few hepatocytes around the central vein. From 3 to 24 hours after injection, the area of SAA-positive hepatocytes extended to the midlobular zone and then gradually decreased in size. On electron microscopy, SAA was present in rough endoplasmic reticulum, smooth endoplasmic reticulum, lipid droplets, and vesicles containing lipid particles. Some lipid particles were positively stained in the space of Disse. From 6 to 36 hours after injection, SAA appeared in the proximal convoluted tubules of the kidney, where SAA was associated with fine particles at the brush border and with multivesicular bodies and lipid droplets in the cytoplasm. Between 18 and 24 hours after injection, SAA appeared in periportal to midlobular hepatocytes as granular deposits. SAA was localized in the cytoplasm around lipid droplets and small vesicles. These vesicles were recognized as endocytic vesicles by their localization close to or fused with peroxisomes and lysosomes. In the kidney SAA was distributed in mesangial cells, podocytes, and tubular interstitium. Localization of SAA in amyloid-laden mice that had received 30 casein injections was almost the same as that in ones that had received a single injection, i.e., hepatocytes, proximal convoluted tubules, and glomeruli. Amyloid deposition was detected near or at the same sites as those where SAA later appeared. Based upon these results we postulate that: Hepatocytes participate in not only the production, but also in the degradation of SAA. At least part of SAA is secreted as a lipid combined form. Circulating SAA is filtered through the glomeruli into Bowman's space and reabsorbed from the proximal convoluted tubules. SAA is metabolized at the same sites even in the amyloid laden state and amyloid is deposited in close relation to the catabolic pathway of SAA.
采用直接过氧化物酶标记抗体法观察血清淀粉样蛋白A（SAA）的定位。通过单次皮下注射酪蛋白在小鼠体内诱导产生SAA。注射前，在中央静脉周围的少数肝细胞中检测到微量SAA。注射后3至24小时，SAA阳性肝细胞的区域扩展至小叶中区，然后逐渐缩小。在电子显微镜下，SAA存在于粗面内质网、滑面内质网、脂滴以及含有脂质颗粒的囊泡中。一些脂质颗粒在狄氏间隙中呈阳性染色。注射后6至36小时，SAA出现在肾脏的近端小管中，在那里SAA与刷状缘的细颗粒以及细胞质中的多囊泡体和脂滴相关。注射后18至24小时，SAA以颗粒状沉积物形式出现在汇管区至小叶中区的肝细胞中。SAA定位于脂滴和小囊泡周围的细胞质中。这些囊泡因其靠近过氧化物酶体和溶酶体或与之融合的定位而被识别为内吞囊泡。在肾脏中，SAA分布于系膜细胞、足细胞和肾小管间质。接受30次酪蛋白注射的淀粉样变小鼠中SAA的定位与接受单次注射的小鼠几乎相同，即肝细胞、近端小管和肾小球。在SAA后来出现的部位附近或相同部位检测到淀粉样沉积。基于这些结果，我们推测：肝细胞不仅参与SAA的产生，还参与其降解。至少部分SAA以脂质结合形式分泌。循环中的SAA通过肾小球滤过进入鲍曼间隙，并从近端小管重吸收。即使在淀粉样变状态下，SAA也在相同部位代谢，且淀粉样物质与SAA的分解代谢途径密切相关沉积。
