Synthesis, metabolism andfibrillogenesis of serum amyloid A bymonocytes or macrophages

血清淀粉样蛋白A （SAA）是AA蛋白的前体，是反应性淀粉样蛋白沉积的主要成分。巨噬细胞在AA纤维形成中起核心作用，细胞可以产生SAA。本研究以单核白血病细胞系THP-1为巨噬细胞模型，考察了单核/巨噬细胞合成SAA的几个特征。细胞主要通过IL-1分泌SAA，糖皮质激素对SAA的产生至关重要。事实上，在糖皮质激素存在的情况下，THP-1可以在含有小牛血清的普通培养基的培养条件下产生SAA。这些特征与SAA的主要产生者肝细胞有很大的不同。这些结果表明，在生理条件下，巨噬细胞可能产生SAA，其他非肝组织也可能产生SAA，尽管其数量与炎症时肝脏产生的SAA数量无法相比。当糖皮质激素用于治疗时，巨噬细胞利用自身产生的SAA形成纤维的可能性不能排除。接下来，在THP-1培养基中加入SAA蛋白后，评估THP-1细胞是否能制造淀粉样原纤维。尝试了几种条件，但未能产生刚果红正极材料。SAA的加入使THP-1细胞高度聚集，这可能代表了SAA作为趋化剂的特性。对于原纤维的形成，可能需要进一步改变实验条件。

Serum amyloid A (SAA) is a precursor of AA proteins, the main constituent of reactive amyloid deposits. Macrophages play a central role in AA fibrillogenesis and the cells can produce SAA. In this study, using a monocytic leukemia cell line THP-1 as a model of macrophages, several features in SAA synthesis by monocytes/macrophages were examined. The cells secrete SAA mainly by IL-1 and glucocorticoid is critical for SAA production. Indeed, in the presence of glucocorticoid, THP-1 can produce SAA under the culture condition using common media containing calf serum. These features are quite different from those of hepatocytes, the main producer of SAA. These results imply that SAA may be produced by macrophages, and possibly other non-hepatic tissues under the physiological conditions although the amount is not comparable with that from the liver at inflammation. The possibility that macrophages utilize self-produced SAA in fibril formation when glucocorticoid is used therapeutically cannot be ruled out. Next, whether or not THP-1 cells can make amyloid fibrils when SAA proteins are added to its culture media was assessed. Several conditions were attempted, but failed to yield congo red positive materials. THP-1 cells were highly aggregated by the addition of SAA, it may represent the feature of SAA as chemoattractant. For fibrils formation, further alteration of experimental conditions may be necessary.