Ding Xin, Liu Yingye, Yang Mu, Li Lin, Miyahara Hiroki, Dai Jian, Xu Zhe, Matsumoto Kiyoshi, Mori Masayuki, Higuchi Keiichi, Sawashita Jinko
Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto-shi, Nagano 390-8621, Japan.
Division of Animal Research, Research Center for Supports to Advanced Science, Shinshu University, 3-1-1 Asahi, Matsumoto-shi, Nagano 390-8621, Japan.
Exp Anim. 2018 May 10;67(2):105-115. doi: 10.1538/expanim.17-0082. Epub 2017 Oct 30.
Mouse senile amyloidosis is a disorder in which apolipoprotein A-II (APOA2) deposits as amyloid fibrils (AApoAII) in many organs. We previously reported that AApoAII amyloidosis can be transmitted by feces, milk, saliva and muscle originating from mice with amyloid deposition. In this study, the ability of blood components to transmit amyloidosis was evaluated in our model system. Blood samples were collected from SAMR1.SAMP1-Apoa2 amyloid-laden or amyloidosis-negative mice. The samples were fractionated into plasma, white blood cell (WBC) and red blood cell (RBC) fractions. Portions of each were further separated into soluble and insoluble fractions. These fractions were then injected into recipient mice to determine amyloidosis-induction activities (AIA). The WBC and RBC fractions from amyloid-laden mice but not from amyloidosis-negative mice induced AApoAII amyloid deposition in the recipients. The AIA of WBC fraction could be attributed to AApoAII amyloid fibrils because amyloid fibril-like materials and APOA2 antiserum-reactive proteins were observed in the insoluble fraction of the blood cells. Unexpectedly, the plasma of AApoAII amyloidosis-negative as well as amyloid-laden mice showed AIA, suggesting the presence of substances in mouse plasma other than AApoAII fibrils that could induce amyloid deposition. These results indicated that AApoAII amyloidosis could be transmitted across tissues and between individuals through blood cells.
小鼠老年性淀粉样变性是一种载脂蛋白A-II（APOA2）以淀粉样原纤维（AApoAII）形式沉积于多个器官的疾病。我们之前报道过，AApoAII淀粉样变性可通过来自有淀粉样沉积的小鼠的粪便、乳汁、唾液和肌肉传播。在本研究中，我们在模型系统中评估了血液成分传播淀粉样变性的能力。从SAMR1.SAMP1-Apoa2淀粉样变负荷小鼠或淀粉样变性阴性小鼠采集血样。将样本分离为血浆、白细胞（WBC）和红细胞（RBC）组分。各组分的一部分进一步分离为可溶和不可溶组分。然后将这些组分注射到受体小鼠体内，以确定淀粉样变性诱导活性（AIA）。来自淀粉样变负荷小鼠而非淀粉样变性阴性小鼠的WBC和RBC组分在受体中诱导了AApoAII淀粉样沉积。WBC组分的AIA可归因于AApoAII淀粉样原纤维，因为在血细胞的不可溶组分中观察到了淀粉样原纤维样物质和APOA2抗血清反应性蛋白。出乎意料的是，AApoAII淀粉样变性阴性小鼠以及淀粉样变负荷小鼠的血浆均显示出AIA，这表明小鼠血浆中除了AApoAII原纤维外，还存在其他可诱导淀粉样沉积的物质。这些结果表明，AApoAII淀粉样变性可通过血细胞在组织间和个体间传播。
