M-ficolin interacts with the long pentraxin PTX3: A novel case of cross-talk between soluble pattern-recognition molecules

Evelyne Gout, Christine Moriscot, Andrea Doni, Chantal Dumestre-Pérard, Monique Lacroix, Julien Pérard, Guy Schoehn, Alberto Mantovani, Gérard J. Arlaud, Nicole M. Thielens

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Abstract

Ficolins and pentraxins are soluble oligomeric pattern-recognition molecules that sense danger signals from pathogens and altered self-cells and might act synergistically in innate immune defense and maintenance of immune tolerance. The interaction of M-ficolin with the long pentraxin pentraxin 3 (PTX3) has been characterized using surface plasmon resonance spectroscopy and electron microscopy. M-ficolin was shown to bind PTX3 with high affinity in the presence of calcium ions. The interaction was abolished in the presence of EDTA and inhibited by N-acetyl-D-glucosamine, indicating involvement of the fibrinogen-like domain of M-ficolin. Removal of sialic acid from the single N-linked carbohydrate of the C-terminal domain of PTX3 abolished the interaction. Likewise, an M-ficolin mutant with impaired sialic acid-binding ability did not interact with PTX3. Interaction was also impaired when using the isolated recognition domain of M-ficolin or the monomeric C-terminal domain of PTX3, indicating requirement for oligomerization of both proteins. Electron microscopy analysis of the M-ficolin-PTX3 complexes revealed that the M-ficolin tetramer bound up to four PTX3 molecules. From a functional point of view, immobilized PTX3 was able to trigger M-ficolin-dependent activation of the lectin complement pathway. These data indicate that interaction of M-ficolin with PTX3 arises from its ability to bind sialylated ligands and thus differs from the binding to the short pentraxin C-reactive protein and from the binding of L-ficolin to PTX3. The M-ficolin-PTX3 interaction described in this study represents a novel case of cross-talk between soluble pattern-recognition molecules, lending further credit to the integrated view of humoral innate immunity that emerged recently.

Original languageEnglish
Pages (from-to)5815-5822
Number of pages8
JournalJournal of Immunology
Volume186
Issue number10
DOIs
Publication statusPublished - May 15 2011

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ASJC Scopus subject areas

  • Immunology

Cite this

Gout, E., Moriscot, C., Doni, A., Dumestre-Pérard, C., Lacroix, M., Pérard, J., Schoehn, G., Mantovani, A., Arlaud, G. J., & Thielens, N. M. (2011). M-ficolin interacts with the long pentraxin PTX3: A novel case of cross-talk between soluble pattern-recognition molecules. Journal of Immunology, 186(10), 5815-5822. https://doi.org/10.4049/jimmunol.1100180