Journal
JOURNAL OF IMMUNOLOGY
Volume 192, Issue 3, Pages 1154-1161Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1301673
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Funding
- European Commission Sixth Framework Program [EC-FP6]
- EC-FP6 grant (European NanoBioPharmaceutics research initiative)
- Prinses Beatrix Fonds [MAR03-0115]
- Francaise contre les Myopathies
- Genmab
- Netherlands Organization for Scientific Research
- Brain Foundation of The Netherlands
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C1q is the initiator of the classical complement pathway and, as such, is essential for efficient opsonization and clearance of pathogens, altered self-structures, and apoptotic cells. The ceramide transporter protein (CERT) and its longer splicing isoform CERTL are known to interact with extracellular matrix components, such as type IV collagen, and with the innate immune protein serum amyloid P. In this article, we report a novel function of CERT in the innate immune response. Both CERT isoforms, when immobilized, were found to bind the globular head region of C1q and to initiate the classical complement pathway, leading to activation of C4 and C3, as well as generation of the membrane attack complex C5b-9. In addition, C1q was shown to bind to endogenous CERTL on the surface of apoptotic cells. These results demonstrate the role of CERTs in innate immunity, especially in the clearance of apoptotic cells.
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