A deficiency in the in vivo clearance of apoptotic cells is a feature of the NOD mouse
A deficiency in the in vivo clearance of apoptotic cells is a feature of the NOD mouse
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DOI：
10.1016/j.jaut.2005.11.006
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发表时间：
2006-03-01
影响因子：
12.8
通讯作者：
Dutz, JP
中科院分区：
文献类型：
--
作者：
O'Brien, BA;Geng, X;Dutz, JP
凋亡细胞清除的缺陷与自身免疫有关。在这里，我们检查了将凋亡胸腺细胞直接注射到 NOD 小鼠和 BALB/c 对照小鼠腹膜后腹膜巨噬细胞吞噬垂死细胞的时间过程。与对照巨噬细胞相比，NOD 小鼠的巨噬细胞在吞噬凋亡胸腺细胞方面表现出严重缺陷。与 BALB/c 或 NOR 对照相比，非肥胖糖尿病小鼠在胸腺细胞凋亡刺激（地塞米松）后也表现出凋亡细胞负荷清除率的降低。此外，与对照品系相比，NOD 小鼠在角质形成细胞凋亡刺激（紫外线，UVB）后表现出凋亡细胞负荷增加。缺乏巨噬细胞吞噬细胞凋亡碎片的动物通常表现出以产生抗核自身抗体（ANA）为特征的自身免疫表型。我们确定增加的凋亡细胞负荷（通过反复暴露于 UVB 照射）是否会加速年轻 NOD 小鼠的这种自身免疫现象。经过反复 UVB 照射后，NOD 小鼠（而非 BALB/c 或 NOR 对照）出现了 ANA。我们认为巨噬细胞清除凋亡细胞的异常使 NOD 小鼠容易产生自身免疫。 (c) 2005 Elsevier Ltd. 保留所有权利。
Deficiencies in apoptotic cell clearance have been linked to autoimmunity. Here we examined the time-course of peritoneal macrophage phagocytosis of dying cells following the direct injection of apoptotic thymocytes into the peritoneum of NOD mice and BALB/c controls. Macrophages from NOD mice demonstrated a profound defect in the phagocytosis of apoptotic thymocytes as compared to control macrophages. Nonobese diabetic mice also demonstrated a decrease in the clearance of apoptotic cell loads following an apoptotic stimulus to thymocytes (dexamethasone) when compared to BALB/c or NOR controls. Further, NOD mice demonstrated an increase in apoptotic cell load following an apoptotic stimulus to keratinocytes (ultraviolet light, UVB) when compared to control strains. Animals deficient in macrophage phagocytosis of apoptotic debris often manifest an autoimmune phenotype characterized by the production of antinuclear autoantibodies (ANA). We determined whether increased apoptotic cell loads (through repeated exposure to UVB irradiation) could accelerate such autoimmune phenomena in young NOD mice. Following repeated UVB irradiation, NOD mice, but not BALB/c or NOR controls, developed ANA. We propose that abnormalities in apoptotic cell clearance by macrophages predispose NOD mice to autoimmunity. (c) 2005 Elsevier Ltd. All rights reserved.