title: M-ficolin interacts with the long pentraxin PTX3: a novel case of cross-talk between soluble pattern-recognition molecules.
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.
authors.affiliation: Commissariat à l'Énergie Atomique, Institut de Biologie Structurale Jean-Pierre Ebel, 38027 Grenoble, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Gout
authors.forename: Christine
authors.initials: C
authors.lastname: Moriscot
authors.forename: Andrea
authors.initials: A
authors.lastname: Doni
authors.forename: Chantal
authors.initials: C
authors.lastname: Dumestre-Pérard
authors.forename: Monique
authors.initials: M
authors.lastname: Lacroix
authors.forename: Julien
authors.initials: J
authors.lastname: Pérard
authors.forename: Guy
authors.initials: G
authors.lastname: Schoehn
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Gérard J
authors.initials: GJ
authors.lastname: Arlaud
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Thielens
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000737:chemistry; D006801:Humans; D007108:Immune Tolerance; D056724:Immunity, Humoral; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008854:Microscopy, Electron; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000683:Serum Amyloid P-Component / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D020349:Surface Plasmon Resonance; D000097604:Ficolins; D000099153:Pentraxins
chemical_list: D000117:Acetylglucosamine; D002097:C-Reactive Protein; D002118:Calcium; D037102:Lectins; D008024:Ligands; D050505:Mutant Proteins; D019158:N-Acetylneuraminic Acid; D000683:Serum Amyloid P-Component; D000097604:Ficolins; D000099153:Pentraxins