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Publication : A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo.

First Author  Taylor PR Year  2000
Journal  J Exp Med Volume  192
Issue  3 Pages  359-66
PubMed ID  10934224 Mgi Jnum  J:63875
Mgi Id  MGI:1861881 Doi  10.1084/jem.192.3.359
Citation  Taylor PR, et al. (2000) A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 192(3):359-66
abstractText  The strongest susceptibility genes for the development of systemic lupus erythematosus (SLE) in humans are null mutants of classical pathway complement proteins. There is a hierarchy of disease susceptibility and severity according to the position of the missing protein in the activation pathway, with the severest disease associated with C1q deficiency. Here we demonstrate, using novel in vivo models of apoptotic cell clearance during sterile peritonitis, a similar hierarchical role for classical pathway complement proteins in vivo in the clearance of apoptotic cells by macrophages. Our results constitute the first demonstration of an impairment in the phagocytosis of apoptotic cells by macrophages in vivo in a mammalian system. Apoptotic cells are thought to be a major source of the autoantigens of SLE, and impairment of their removal by complement may explain the link between hereditary complement deficiency and the development of SLE.
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