Mori Y, Akikusa B, Mori T, Ueda S, Iesato K, Yoshida H, Ogawa M, Kato I, Wakashin Y, Wakashin M
J Exp Med. 1986 Jun 1;163(6):1553-65. doi: 10.1084/jem.163.6.1553.
Systemic amyloidosis was induced consistently in mice by intramuscular injection of syngeneic organ (liver and kidney) extracts mixed with CFA six times at weekly intervals. Syngeneic organ extract with CFA also induced amyloidosis of a lesser degree. All three strains of mice (C57BL/6, C3H/He, and BALB/c) injected with a syngeneic liver extract mixed with CFA developed systemic amyloidosis; the most prominent amyloid deposition occurred in C57BL/6 (B6) mice, followed by C3H/He and BALB/c. The amyloid substance deposited in these animals was identified as mouse amyloid A protein (AA). Furthermore, an organ specificity of the immunogen in inducing amyloidosis was suggested with liver and kidney extracts. Primed spleen cells of the immunized B6 mice were fractionated by a nylon-wool column and injected to normal recipient mice via the tail vein. Organs of the recipient mice developed systemic amyloidosis 8 wk after the transfer, and the most prominent histological changes occurred in the recipient mice given nylon-wool column adherent spleen cells. Using anti-Thy-1,2; Ly-1; Ly-2, antibody and complement, it was suggested that T cells, especially Ly-1,2,3+ T cell populations in the primed nylon-wool adherent cells, play an important role in the induction of systemic amyloidosis. It was shown further that the amyloidosis-inducing substance in liver extract was composed of unstable proteins or protein-bound substance.
通过每周一次、共六次肌肉注射同基因器官(肝脏和肾脏)提取物与完全弗氏佐剂(CFA)的混合物,可在小鼠中持续诱导出系统性淀粉样变性。同基因器官提取物与CFA也能诱导程度较轻的淀粉样变性。给所有三个品系的小鼠(C57BL/6、C3H/He和BALB/c)注射同基因肝脏提取物与CFA的混合物后,均出现了系统性淀粉样变性;最显著的淀粉样蛋白沉积发生在C57BL/6(B6)小鼠中,其次是C3H/He和BALB/c。沉积在这些动物体内的淀粉样物质被鉴定为小鼠淀粉样蛋白A(AA)。此外,肝脏和肾脏提取物表明免疫原在诱导淀粉样变性方面具有器官特异性。将免疫后的B6小鼠的致敏脾细胞通过尼龙毛柱进行分离,并经尾静脉注射到正常受体小鼠体内。受体小鼠的器官在转移后8周出现系统性淀粉样变性,且在接受尼龙毛柱黏附脾细胞的受体小鼠中出现最显著的组织学变化。使用抗Thy-1,2;Ly-1;Ly-2,抗体和补体,表明T细胞,尤其是致敏尼龙毛黏附细胞中的Ly-1,2,3+ T细胞群体,在系统性淀粉样变性的诱导中起重要作用。进一步表明,肝脏提取物中诱导淀粉样变性的物质由不稳定蛋白质或蛋白质结合物质组成。