AMYLOIDOGENESIS - ONE SERUM AMYLOID-A ISOTYPE IS SELECTIVELY REMOVED FROM THE CIRCULATION
AMYLOIDOGENESIS - ONE SERUM AMYLOID-A ISOTYPE IS SELECTIVELY REMOVED FROM THE CIRCULATION
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DOI：
10.1084/jem.163.3.499
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发表时间：
1986-03-01
影响因子：
15.3
通讯作者：
BENDITT, EP
中科院分区：
文献类型：
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作者：
MEEK, RL;HOFFMAN, JS;BENDITT, EP
在A型淀粉样变性中发现的纤维沉积只来自三种血清淀粉样蛋白A(SAA)基因产物中的一种，即SAA2。为了探讨SAA同型特异性淀粉样蛋白AA沉积的机制，对CBA小鼠在酪蛋白诱导淀粉样变性过程中血清淀粉样蛋白的分子动力学进行了研究。在20d的淀粉样蛋白诱导过程中，检测肝脏SAA1和SAA2的mRNA水平、肝细胞特异性蛋白质合成和分泌率以及血清水平。我们观察到：在第5天，小鼠的脾中出现少量的淀粉样物质，并在随后的15天内稳步增加，到第20天时已占到脾体积的近30%。在诱导形成淀粉样蛋白的过程中，任何时候都没有在脾中检测到SAA mRNA。血清总SAA水平在我们开始酪蛋白治疗后1天达到峰值，因此下降。这一下降完全是由于SAA2的急剧下降，而SAA1水平在整个过程中几乎保持不变。体外翻译测定的肝脏SAA2/SAA1mRNA的比值在20d期间保持不变，新鲜分离的肝细胞合成和分泌的SAA1和SAA2的数量也保持不变。这些数据表明，SAA2来源的淀粉样蛋白A的沉积不是由于脾内局部产生SAA，也不是由于与SAA1相比SAA2产生过多，而是涉及SAA2从SAA1和SAA2的循环池中选择性和加速地清除。
The deposits of fibrils found in amyloidosis of the A type are derived from only one of the three serum amyloid A (SAA) gene products, namely SAA2. In order to explore the mechanism of SAA isotype-specific amyloid protein AA depositon, the molecular kinetics of the serum amyloid proteins were examined in CBA mice during casein induction of amyloidosis. The presence of SAA mRNA in spleen was searched for; hepatic SAA1 and SAA2 mRNA levels, rates of specific protein synthesis and secretion by hepatocytes, and serum levels were measured during a 20-d period of amyloid induction. We observed the following: small amounts of amyloid substance appeared in the spleen by day 5 and increased steadily over the ensuing 15 d to occupy nearly 30% of splenic volume by day 20. No SAA mRNA was detected in spleen at any time during induction of amyloid formation. Total serum SAA levels peaked 1 d after we began casein treatment, and therefore declined. This decline was accounted for entirely by a dramatic fall in SAA2, while SAA1 levels remained nearly constant throughout. The ratios of hepatic SAA2:SAA1 mRNA, as determined by in vitro translation, remained constant during the 20-d period, as did amounts of SAA1 and SAA2 synthesized and secreted by freshly isolated hepatocytes. These data indicate that the deposition of amyloid A protein derived from SAA2 is not due to local SAA production in spleen, nor excessive SAA2 production compared with SAA1, but involves the selective and accelerated removal of SAA2 from the circulating pool of both SAA1 and SAA2.