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.
Licht
R
R
Division of Nephrology, University Medical Centre Nijmegen, The Netherlands.
Jacobs
C W
CW
Tax
W J
WJ
Berden
J H
JH
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