Properdin Binds to Late Apoptotic and Necrotic Cells Independently of C3b and Regulates Alternative Pathway Complement Activation

Cells that undergo apoptosis or necrosis are promptly removed by phagocytes. Soluble opsonins such as complement can opsonize dying cells, thereby promoting their removal by phagocytes and modulating the immune response. The pivotal role of the complement system in the handling of dying cells has be...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2008-06, Vol.180 (11), p.7613-7621
Main Authors: Xu, Wei, Berger, Stefan P, Trouw, Leendert A, de Boer, Hetty C, Schlagwein, Nicole, Mutsaers, Chantal, Daha, Mohamed R, van Kooten, Cees
Format: Article
Language:English
Subjects:
Apoptosis
Cell Line, Tumor
Complement C1q - immunology
Complement C1q - metabolism
Complement C3 Convertase, Alternative Pathway
Complement C3b - immunology
Complement C3b - metabolism
Complement Pathway, Alternative
Humans
Immunologic Factors - immunology
Immunologic Factors - metabolism
Jurkat Cells
Necrosis
Phagocytosis
Properdin - immunology
Properdin - metabolism
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Summary:Cells that undergo apoptosis or necrosis are promptly removed by phagocytes. Soluble opsonins such as complement can opsonize dying cells, thereby promoting their removal by phagocytes and modulating the immune response. The pivotal role of the complement system in the handling of dying cells has been demonstrated for the classical pathway (via C1q) and lectin pathway (via mannose-binding lectin and ficolin). Herein we report that the only known naturally occurring positive regulator of complement, properdin, binds predominantly to late apoptotic and necrotic cells, but not to early apoptotic cells. This binding occurs independently of C3b, which is additional to the standard model wherein properdin binds to preexisting clusters of C3b on targets and stabilizes the convertase C3bBb. By binding to late apoptotic or necrotic cells, properdin serves as a focal point for local amplification of alternative pathway complement activation. Furthermore, properdin exhibits a strong interaction with DNA that is exposed on the late stage of dying cells. Our data indicate that direct recognition of dying cells by properdin is essential to drive alternative pathway complement activation.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.180.11.7613