Synthesis, metabolism andfibrillogenesis of serum amyloid A bymonocytes or macrophages

单核细胞或巨噬细胞血清淀粉样蛋白A的合成、代谢和原纤维形成

• 批准号: 12672251
• 负责人: YAMADA Toshiyuki
• 金额: $ 1.79万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672251/
• 关键词: serum amyloid A; amyloidosis; monocyte; macrophage; inflammation; fibrillogenesis; glucocorticoid; 炎症; SAA; アミロイド線維; 細胞株; サイトカイン; アミロイド沈着; コルチコステロイド; THP-1

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.

血清淀粉样蛋白A（SAA）是AA蛋白的前体，AA蛋白是反应性淀粉样蛋白沉积的主要成分。巨噬细胞在AA纤维形成中起着重要作用，并且细胞可以产生SAA。在这项研究中，使用单核细胞白血病细胞系THP-1作为巨噬细胞的模型，SAA合成的单核细胞/巨噬细胞的几个功能进行了检查。细胞主要通过IL-1分泌SAA，糖皮质激素是SAA产生的关键。事实上，在糖皮质激素存在下，THP-1可以在使用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的主要生产者肝细胞的特征完全不同。这些结果意味着SAA可能由巨噬细胞产生，并且可能在生理条件下由其他非肝组织产生，尽管其量与炎症时来自肝脏的量不可比较。不能排除当糖皮质激素用于治疗时巨噬细胞利用自身产生的SAA形成原纤维的可能性。接下来，评估当SAA蛋白质添加到其培养基中时THP-1细胞是否可以产生淀粉样蛋白原纤维。尝试了几种条件，但未能产生刚果红阳性材料。加入SAA后THP-1细胞高度聚集，这可能代表SAA作为化学引诱剂的特征。对于原纤维的形成，可能需要进一步改变实验条件。

项目成果

Yamada T, Okuda Y, Takasugi K, Wang L, Marks D, Benson MD, Kluve-Beckerman B: "An allele of serum amyloid A1 associated with amyloidosis in both Japanese and Caucasians"Amyloid : J Prot Fold Dis. 10 (2003)

Yamada T、Okuda Y、Takasugi K、Wang L、Marks D、Benson MD、Kluve-Beckerman B：“与日本人和白种人淀粉样变性相关的血清淀粉样蛋白 A1 等位基因”淀粉样蛋白：J Prot Fold Dis。

Yamada T, Sotoh T: "Changes in individual serum beta2-microglobulin in regular hemodialysis"Ckinical Nephrology. (2003)

Yamada T、Sotoh T：“常规血液透析中个体血清 β2-微球蛋白的变化”Ckinical Nephrology。

Yamada T 他: "Serum amyloid A secretion from monocytic leukemia cell line THP-1 and cultured human peripheral monocytes."Scandinavian Journal of Immunology. 52. 7-12 (2000)

Yamada T 等人：“单核细胞白血病细胞系 THP-1 和培养的人外周单核细胞的血清淀粉样蛋白 A 分泌。”斯堪的纳维亚免疫学杂志 52. 7-12 (2000)。

山田 俊幸: "An allele of serum amyloid A1 associated with amyloidosis in both Japanese and Caucasians"Amyloid. (in press).

Toshiyuki Yamada：“与日本人和白种人淀粉样变性相关的血清淀粉样蛋白 A1 的等位基因”淀粉样蛋白（正在出版）。

Yamada T, Okuda Y, Takasugi K, Itoh K, Igari J: "Relative serum amyloid A (SAA) values : the influence of SAA1 genotypes and corticosteroid treatment in Japanese patients with rheumatoid arthritis"Ann Rheum Dis. 60. 124-127 (2001)

Yamada T、Okuda Y、Takasugi K、Itoh K、Igari J：“相对血清淀粉样蛋白 A (SAA) 值：SAA1 基因型和皮质类固醇治疗对日本类风湿性关节炎患者的影响”Ann Rheum Dis。