Immunohistochemical detection of serum amyloid A protein in the liver and the kidney after casein injection.

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.