Secreted M-Ficolin Anchors onto Monocyte Transmembrane G Protein-Coupled Receptor 43 and Cross Talks with Plasma C-Reactive Protein to Mediate Immune Signaling and Regulate Host Defense

Zhang, Jing; Yang, Lifeng; Ang, Zhiwei; Yoong, Sia Lee; Tran, Thi Thu Thuy; Anand, Ganesh S.; Tan, Nguan Soon; Ho, Bow; Ding, Jeak Ling

doi:10.4049/jimmunol.1001225

Cited by 58 publications

(54 citation statements)

References 49 publications

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“…In addition, recent studies have pointed out that the interaction of M-ficolin with CRP is sensitive to pH-induced conformational changes, the binding site for CRP being distinct from the GlcNAc binding site at pH 7.4, but similar at pH 6.5 (21). In this respect, it should be mentioned that the PTX3-M-ficolin interaction characterized in this study is also likely to be influenced by a decrease in pH, because the acetylbinding pocket is dislocated at pH 5.6 (32).…”

Section: Discussionmentioning

confidence: 99%

“…Its ability to bind sialic acid (14,19) has been proposed to account for its tethering to host cell surfaces (20). However, it was reported recently that anchoring of M-ficolin on the monocyte membrane is mediated via a transmembrane receptor, G protein-coupled receptor 43 (21). Previous studies have shown the ability of monocyte M-ficolin to bind certain bacteria (16), and the complement-activating capacity of the recombinant protein has been demonstrated using immobilized acetylated albumin conjugates (14,19,22).…”

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confidence: 99%

“…M-ficolin has been reported to interact with CRP and PTX3 (10,21,28,31), and binding to CRP was shown to involve the Cterminal part of its FBG domain (21,31). Moreover, it has been proposed recently that interaction of CRP with the membraneanchored M-ficolin/G protein-coupled receptor 43 complex regulates immune signaling (21).…”

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confidence: 99%

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M-Ficolin Interacts with the Long Pentraxin PTX3: A Novel Case of Cross-Talk between Soluble Pattern-Recognition Molecules

Gout

Moriscot

Doni

et al. 2011

The Journal of Immunology

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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.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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M-Ficolin Interacts with the Long Pentraxin PTX3: A Novel Case of Cross-Talk between Soluble Pattern-Recognition Molecules

Gout

Moriscot

Doni

et al. 2011

The Journal of Immunology

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“…Recently, it has been shown that ficolin-1 interacts with the short pentraxin CRP via a flexible binding site on ficolin-1, which could be transduced in a pH-sensitive fashion. Under physiological pH, CRP associates weakly with the FBG of ficolin-1 and exposes the PAMP binding site of the FBG to pathogens, whereas under acidic pH, ficolin-1 alters conformation of the binding site on FBG, so that CRP is more readily accessible to ficolin-1, which consequently blocks PAMP-ficolin-1 interaction (28). Therefore, we assessed whether a pH-dependent conformational switch of ficolin-1 may affect the interaction between ficolin-1 and PTX3.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, ficolin-1 recognizes acetylated compounds and sialic acid-containing carbohydrates on some capsulated bacteria (18,19,26,27). Moreover, it has been suggested that a potential in-teraction between the collagen-like domain of ficolin-1 and monocytes is mediated via interaction with the G protein-coupled receptor 43 (28). However, little is known about the endogenous and microbial ligands of ficolin-1 and the physiological role of ficolin-1 in infection and inflammation.…”

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confidence: 99%

Ficolin-1–PTX3 Complex Formation Promotes Clearance of Altered Self-Cells and Modulates IL-8 Production

Jie

Doni

Romani

et al. 2013

The Journal of Immunology

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The long pentraxin 3 (PTX3) has been shown to be important in maintaining internal tissue homeostasis and in protecting against fungal Aspergillus fumigatus infection. However, the molecular mechanisms of how these functions are elicited are poorly delineated. Ficolin-1 is a soluble pattern recognition molecule that interacts with PTX3. We hypothesized that heterocomplexes between ficolin-1 and PTX3 might mediate the signals necessary for sequestration of altered self-cells and A. fumigatus. We were able to show that ficolin-1 interacts with PTX3 via its fibrinogen-like domain. The interaction was affected in a pH- and divalent cation–sensitive manner. The primary binding site for ficolin-1 on PTX3 was located in the N-terminal domain portion of PTX3. Ficolin-1 and PTX3 heterocomplex formation occurred on dying host cells, but not on A. fumigatus. The heterocomplex formation was a prerequisite for enhancement of phagocytosis by human monocyte–derived macrophages and downregulation of IL-8 production during phagocytosis. On A. fumigatus, PTX3 exposed the C-terminal portion of the molecule, probably resulting in steric hindrance of ficolin-1 interaction with PTX3. These results demonstrate that ficolin-1 and PTX3 heterocomplex formation acts as a noninflammatory “find me and eat me” signal to sequester altered-host cells. The fact that the ficolin-1–PTX3 complex formation did not occur on A. fumigatus shows that PTX3 uses different molecular effector mechanisms, depending on which domains it exposes during ligand interaction.

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Ficolins

Takahashi

Thiel

2013

Encyclopedia of Life Sciences

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Ficolins are innate immune pattern‐recognition molecules. The name of ficolin was derived from its basic structure, consisting of a collagen‐like domain and a fibrinogen‐like domain (FBG). The FBG preferably recognises acetylated compounds. Humans have three homologous proteins: H‐ficolin (or ficolin‐3), L‐ficolin (or ficolin‐2) and M‐ficolin (or ficolin‐1). Mice have ficolin‐A and ficolin‐B, which are homologous to L‐ficolin and M‐ficolin, respectively, whereas a murine homologue of H‐ficolin is absent. Ficolin genes are germinally present and, therefore, their proteins are expressed at healthy state and are circulating in blood or localised in organs, affording an instant host protection. Ficolins are homologous to collectins structurally and functionally but has a difference in target recognition. Ficolins, like collectins, play important roles in innate immunity as activators of the lectin pathway of the complement system. Key Concepts: Ficolins are molecules of innate immunity, which is the first line of host defence mechanism and is fully functional throughout the body and life regardless of health. Ficolins are similar to collectins in their structures and biologic functions with a major difference that target recognition is through fibrinogen‐like domain unlike carbohydrate recognition domain of collectins. Ficolins are pattern‐recognition molecules, which are able to identify invading pathogens and abnormal cells and tissues, in addition to normal cells, which are not recognised by collectins. Selected genetic mutations affect functions of ficolins and are associated with reduced host defence mechanisms. Some ficolins may be a disease modifier as deficiency itself may cause no problem, whereas it may have adverse effect depending on types of disease, infection or injury. Ficolins have structural and functional homology to collectins and may share and substitute functions in host defence.

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Secreted M-Ficolin Anchors onto Monocyte Transmembrane G Protein-Coupled Receptor 43 and Cross Talks with Plasma C-Reactive Protein to Mediate Immune Signaling and Regulate Host Defense

Cited by 58 publications

References 49 publications

M-Ficolin Interacts with the Long Pentraxin PTX3: A Novel Case of Cross-Talk between Soluble Pattern-Recognition Molecules

M-Ficolin Interacts with the Long Pentraxin PTX3: A Novel Case of Cross-Talk between Soluble Pattern-Recognition Molecules

Ficolin-1–PTX3 Complex Formation Promotes Clearance of Altered Self-Cells and Modulates IL-8 Production

Ficolins

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