A deficiency in the in vivo clearance of apoptotic cells is a feature of the NOD mouse

被引:92
作者
O'Brien, BA
Geng, X
Orteu, CH
Huang, YQ
Ghoreishi, M
Zhang, YQ
Bush, JA
Li, G
Finegood, DT
Dutz, JP
机构
[1] Univ British Columbia, Dept Med, Div Dermatol, Vancouver, BC V5Z 4E8, Canada
[2] Univ Technol Sydney, Sydney, NSW 2007, Australia
[3] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada
[4] Royal Free Hosp, London NW3 2QG, England
基金
加拿大健康研究院;
关键词
clearance; macrophages; autoimmunity; diabetes; apoptosis;
D O I
10.1016/j.jaut.2005.11.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:104 / 115
页数:12
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