No constitutive defect in phagocytosis of apoptotic cells by resident peritoneal macrophages from pre-morbid lupus mice

被引:22
作者
Licht, R [1 ]
Jacobs, CWM [1 ]
Tax, WJM [1 ]
Berden, JHM [1 ]
机构
[1] Univ Nijmegen, Med Ctr, Div Nephrol 545, NL-6500 HB Nijmegen, Netherlands
关键词
phagocytosis; apoptosis; mouse; lupus erythematosus;
D O I
10.1191/096120301672276558
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Antibodies against nucleosomes are a hallmark of systemic lupus erythematosus (SLE). Nucleosomes are uniquely formed during apoptosis, through cleavage of chromatin by nucleases. Increased exposure of nucleosomes to the immune system could play a role in the induction of the autoimmune repertoire in SLE. To determine whether there exists a constitutive defect in the clearance of apoptotic cells, resident peritoneal macrophages from pre-morbid SLE-prone MRL and New Zealand (NZ) mice were analysed for their efficacy to phagocytose apoptotic cells in vitro. Although differences in phagocytic efficacy of up to 50% between different strains of mice were found, these were not related to SLE development. To evaluate whether macrophages from SLE-prone mice are more susceptible to phagocytic 'exhaustion', resident peritoneal macrophages were challenged by 20 h of additional culture in the presence of apoptotic cells. In both lupus and control strains this led to an increased capacity to phagocytose fresh apoptotic cells (increase between 15 and 92%). As a control, macrophages from all strains were also exposed to 20h of additional culture without apoptotic cells. Under this condition resident peritoneal macrophages from all SLE-prone strains, and of the SLE-parental strain NZB, displayed a significant decrease in their efficacy to phagocytose apoptotic cells (decrease between 16 and 55%). Together, these findings do not support the hypothesis that a constitutive defect in the clearance of apoptotic cells, as evaluated by testing resident peritoneal macrophages, plays an important role in the induction of SLE.
引用
收藏
页码:102 / 107
页数:6
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