Macrophages in the reticuloendothelial system inhibit early induction stages of mouse apolipoprotein A-II amyloidosis
Macrophages in the reticuloendothelial system inhibit early induction stages of mouse apolipoprotein A-II amyloidosis
复制标题
网状内皮系统中的巨噬细胞抑制小鼠载脂蛋白 A-II 淀粉样变性的早期诱导阶段
DOI：
10.1080/13506129.2022.2153667
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发表时间：
2022
期刊：
影响因子：
5.5
通讯作者：
Higuchi Keiichi
中科院分区：
文献类型：
--
作者：
Miyahara Hiroki;Dai Jian;Li Ying;Cui Xiaoran;Takeuchi Hibiki;Hachiya Naomi;Kametani Fuyuki;Yazaki Masahide;Mori Masayuki;Higuchi Keiichi
淀粉样变性是指一组退行性疾病，其特征在于在各种器官中沉积错误折叠的蛋白原纤维。沉积的淀粉样蛋白可能被吞噬细胞依赖的先天免疫系统清除;然而，疾病进展过程中的确切机制仍不清楚。我们在此使用诱导型载脂蛋白A-II淀粉样变性模型小鼠研究了巨噬细胞对淀粉样蛋白降解和疾病进展的作用。腹腔注射AApoAII淀粉样蛋白可有效地被肝脏和脾脏中的网状内皮巨噬细胞吞噬，并在24 h内消失。虽然培养的小鼠巨噬细胞降解AApoAII纤维内体-溶酶体途径，AApoAII纤维降低细胞活力和吞噬能力。此外，在诱导AApoAII之前网状内皮巨噬细胞的耗竭显著增加了肝脏和脾脏AApoAII沉积。这些结果突出了网状内皮巨噬细胞在发病早期阶段的生理作用，并建议维持吞噬细胞的完整性作为抑制疾病进展的治疗策略。
Amyloidosis refers to a group of degenerative diseases that are characterized by the deposition of misfolded protein fibrils in various organs. Deposited amyloid may be removed by a phagocyte-dependent innate immune system; however, the precise mechanisms during disease progression remain unclear. We herein investigated the properties of macrophages that contribute to amyloid degradation and disease progression using inducible apolipoprotein A-II amyloidosis model mice. Intravenously injected AApoAII amyloid was efficiently engulfed by reticuloendothelial macrophages in the liver and spleen and disappeared by 24 h. While cultured murine macrophages degraded AApoAIIviathe endosomal-lysosomal pathway, AApoAII fibrils reduced cell viability and phagocytic capacity. Furthermore, the depletion of reticuloendothelial macrophages before the induction of AApoAII markedly increased hepatic and splenic AApoAII deposition. These results highlight the physiological role of reticuloendothelial macrophages in the early stages of pathogenesis and suggest the maintenance of phagocytic integrity as a therapeutic strategy to inhibit disease progression.