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用于探究血清淀粉样蛋白A淀粉样变发展的位点特异性抗体的产生及应用

Generation and use of site-specific antibodies to serum amyloid A for probing amyloid A development.

作者信息

Miura K, Ju S T, Cohen A S, Shirahama T

机构信息

Arthritis Center, Boston University School of Medicine, MA 02118.

出版信息

J Immunol. 1990 Jan 15;144(2):610-3.

PMID:2295803
Abstract

Serum amyloid A (SAA) is an acute phase reactant and the putative precursor of an amyloid fibril protein (AA). During amyloidogenesis in mice, the C-terminal portion of SAA that consists of 28 amino acids is cleaved off to produce the 75 amino acid AA. Of three known isotypes of SAA, SAA2 has been identified as amyloidogenic. For differential immunologic recognition of SAA and AA, antisera were generated in rabbits against AA protein and a synthetic peptide corresponding to the C-terminal (amino acids 84 to 103) of murine SAA2. The anti-AA antiserum reacted with AA and SAA, but the anti-peptide antiserum reacted with SAA only. Immunohistochemically anti-peptide antiserum predominantly stained the rims of murine amyloid deposits. In contrast, anti-AA antiserum generated an overall homogeneous staining of amyloid deposits. The data lend support to a view that SAA are concentrated in the vicinity of the surrounding cells (mostly macrophages) where they are processed to AA, or that SAA are deposited initially as components of the amyloid fibrils onto the outside margin of amyloid deposits and the C-terminus is cleaved off as maturation of the amyloid fibril progresses.

摘要

血清淀粉样蛋白A(SAA)是一种急性期反应物,也是淀粉样纤维蛋白(AA)的假定前体。在小鼠的淀粉样变发生过程中,由28个氨基酸组成的SAA C末端部分被切除,产生75个氨基酸的AA。在已知的三种SAA同种型中,SAA2已被确定具有淀粉样变性。为了对SAA和AA进行差异性免疫识别,用兔抗AA蛋白和与小鼠SAA2 C末端(氨基酸84至103)对应的合成肽制备了抗血清。抗AA抗血清与AA和SAA反应,但抗肽抗血清仅与SAA反应。免疫组织化学显示,抗肽抗血清主要染色小鼠淀粉样沉积物的边缘。相比之下,抗AA抗血清对淀粉样沉积物产生整体均匀染色。这些数据支持这样一种观点,即SAA集中在周围细胞(主要是巨噬细胞)附近,在那里它们被加工成AA,或者SAA最初作为淀粉样纤维的成分沉积在淀粉样沉积物的外缘,随着淀粉样纤维的成熟,C末端被切除。

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Am J Pathol. 2001 Aug;159(2):561-70. doi: 10.1016/S0002-9440(10)61727-0.
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In vitro spontaneous synthesis of beta 2-microglobulin amyloid fibrils in peripheral blood mononuclear cell culture.外周血单个核细胞培养中β2-微球蛋白淀粉样原纤维的体外自发合成
Am J Pathol. 1992 Jul;141(1):241-7.