Complement Activation by Ceramide Transporter Proteins

Gerard H. Bode, Mario Losen, Wim A. Buurman, Robert Veerhuis, Peter C. Molenaar, Harry W. M. Steinbusch, Marc H. De Baets, Mohamed R. Daha, Pilar Martinez-Martinez*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Pages (from-to)1154-1161
JournalJournal of Immunology
Volume192
Issue number3
DOIs
Publication statusPublished - 1 Feb 2014

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