Opsonization with C1q and mannose-binding lectin targets apoptotic cells to dendritic cells.
Deficiencies of early components of the classical complement pathway, particularly C1q, are strongly associated with susceptibility to systemic lupus erythematosus. Recent data link this predisposal to autoimmunity to an inappropriate clearance of apoptotic cells, which could lead to a loss of self-tolerance. In the present study, we demonstrate that opsonization of apoptotic cells with C1q and mannose-binding lectin allows and facilitates their uptake not only by macrophages but also by human immature dendritic cells (DCs). Both C1q and mannose-binding lectin enhance the uptake of apoptotic cells by DCs in a dose-dependent way. The uptake of C1q-opsonized apoptotic cells, but not nonopsonized apoptotic cells, by DCs stimulated the production of IL-6, IL-10, and TNF-alpha, without an effect on IL-12p70. We conclude that these recognition molecules of the complement system do not sequester apoptotic cells from DCs, but rather promote their uptake by immature DCs. Therefore, we propose that early complement components support safe clearance of cellular debris by facilitating phagocytosis and possibly by immunomodulatory mechanisms, thus preventing autoimmunity.
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Alma J
AJ
Nauta
Giuseppe
G
Castellano
Wei
W
Xu
Andrea M
AM
Woltman
Maria C
MC
Borrias
Mohamed R
MR
Daha
Cees
C
van Kooten
Anja
A
Roos
D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D015922:Complement C1q / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D037601:Mannose-Binding Lectin / Q000276:immunology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology; D011951:Receptors, Complement / Q000378:metabolism; D011975:Receptors, Mitogen / Q000378:metabolism
D016207:Cytokines; D037601:Mannose-Binding Lectin; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D011975:Receptors, Mitogen; C032402:complement 1q receptor; D015922:Complement C1q