No constitutive defect in phagocytosis of apoptotic cells by resident peritoneal macrophages from pre-morbid lupus mice.
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 20 h 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.
Division of Nephrology, University Medical Centre Nijmegen, The Netherlands.
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R
Licht
C W
CW
Jacobs
W J
WJ
Tax
J H
JH
Berden
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000473:pathology; D051379:Mice; D010587:Phagocytosis / Q000276:immunology