L-Ficolin Specifically Binds to Lipoteichoic Acid, a Cell Wall Constituent of Gram-Positive Bacteria, and Activates the Lectin Pathway of Complement

Lynch, Nicholas J.; Roscher, Silke; Hartung, Thomas; Morath, Siegfried; Matsushita, Misao; Maennel, Daniela N.; Kuraya, Mikio; Fujita, Teizo; Schwaeble, Wilhelm

doi:10.4049/jimmunol.172.2.1198

Cited by 232 publications

(156 citation statements)

References 31 publications

Supporting

Mentioning

147

Contrasting

Unclassified

Order By: Relevance

“…L-ficolin binds to GlcNAc residue next to galactose at the nonreducing terminal of the oligosaccharide (21). Several reports recently showed that L-ficolin could bind to various acetylated compounds, 1,3-β-D glucan, a molecular marker of yeast and fungal cell walls, lipopolysaccharide (LPS) on gram-negative bacterial species and Lipoteichoic Acid (LTA) on the gram-positive bacteria Staphylococcus aureus and Streplococcus pneumoniae, following the activation of complement (22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

Liu

Ali

et al. 2009

Cell Mol Immunol

View full text Add to dashboard Cite

L-ficolin, one of lectin families, is a recently identified complement factor that initiates lectin pathway of complement. Little is known about its role in viral hepatitis. In the present study, we found that L-ficolin in serum from 103 patients with hepatitis C virus (HCV), were significantly higher than that in 150 healthy controls. We further found that L-ficolin expressions were significantly increased in vitro study by HCV JFH-1 infected human hepatocyte cell line Huh7.5.

show abstract

Section: Introductionmentioning

confidence: 99%

Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

Liu

Ali

et al. 2009

Cell Mol Immunol

View full text Add to dashboard Cite

show abstract

“…The binding ability is inhibited by acetylated compounds, indicating that this protein specifically recognizes acetyl groups (31). L-ficolin activates the lectin complement pathway upon binding to lipoteichoic acid, a cell wall component of all Gram-positive bacteria (32). H-ficolin (synonymous with ficolin-3 or Hakata-antigen) has a primary sequence that is 48% identical to that of L-ficolin and binds to GlcNAc, and D-fucose (14).…”

mentioning

confidence: 99%

Trivalent Recognition Unit of Innate Immunity System

Tanio

Kondo

Sugio

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Ficolins are a kind of pathogen-recognition molecule in the innate immune systems. To investigate the discrimination mechanism between self and non-self by ficolins, we determined the crystal structure of the human M-ficolin fibrinogen-like domain (FD1), which is the ligand-binding domain, at 1.9 Å resolution. Although the FD1 monomer shares a common fold with the fibrinogen ␥ fragment and tachylectin-5A, the Asp-282-Cys-283 peptide bond, which is the predicted ligand-binding site on the C-terminal P domain, is a normal trans bond, unlike the cases of the other two proteins. The trimeric formation of FD1 results in the separation of the three P domains, and the spatial arrangement of the three predicted ligand-binding sites on the trimer is very similar to that of the trimeric collectin, indicating that such an arrangement is generally required for pathogen-recognition. The ligand binding study of FD1 in solution indicated that the recombinant protein binds to N-acetyl-D-glucosamine and the peptide Gly-Pro-Arg-Pro and suggested that the ligand-binding region exhibits a conformational equilibrium involving cis-trans isomerization of the Asp-282-Cys-283 peptide bond. The crystal structure and the ligand binding study of FD1 provide an insight of the self-and non-self discrimination mechanism by ficolins.Surveillance systems of innate immunity are present in all multicellular organisms and play a crucial role in the first line of defense against pathogens. Ficolins, as well as collectins, are one of the most important groups of pattern recognition molecules in the innate immunity systems (1-7) and have been identified in both vertebrates and invertebrates (6). Ficolins are comprised of a collagen-like domain at the N terminus and a fibrinogen-like domain (FBG), 3 which is the sugar-binding site, at the C terminus (8, 9). Collectins, such as mannose-binding lectin (MBL), lung surfactant protein A, and surfactant protein D, also consist of an N-terminal collagen-like domain and a C-terminal carbohydrate-recognition domain (CRD) that binds to certain carbohydrates such as mannose and GlcNAc Ca 2ϩ dependently. The CRD on MBL, surfactant protein A, and surfactant protein D forms a trimeric structure through a triple ␣-helical coiled-coil at a short neck region between the collagen-like domain and the CRD (10 -12). Ficolins also form trimers (8,13,14), although the mechanism of trimerization is unclear. Both ficolins and collectins form trimer-based multimers that are N-terminally linked by disulfide bonds (15). Ficolins and MBL also interact with MBL-associated serine proteases, and their complexes activate the lectin complement pathway (6, 16 -23).Ficolins were originally discovered in porcine uterus membrane extracts as transforming growth factor-␤-binding proteins (24,25). In human, L-ficolin and H-ficolin in serum and M-ficolin in cells have been characterized (9, 14, 26 -29). Lficolin (synonymous with ficolin-2 or Ficolin/P35) binds to GlcNAc (29, 30) and GalNAc (8). The binding ability is inhibited by acetylated c...

show abstract

“…First, in vitro studies show that S. pneumoniae does not have a strong binding affinity for MBL 7. In addition, the immune system has several other, maybe more effective, ways to eliminate S. pneumoniae 13, 35, 36. In fact, the classical and alternative complement pathways have been shown to play a more important role in complement activation in pneumococcus‐infected mice 37…”

Section: Discussionmentioning

confidence: 99%

“…Various polymorphisms in the FCN gene ( FCN2 ) have been described, with two coding SNPs in the fibrinogen‐like domain responsible for binding to micro‐organisms. These coding SNPs lead to, respectively, decreased or increased binding affinity for its substrates 11, 12, 13, 14…”

Section: Introductionmentioning

confidence: 99%

Mannose‐binding lectin and l‐ficolin polymorphisms in patients with community‐acquired pneumonia caused by intracellular pathogens

et al. 2017

View full text Add to dashboard Cite

SummaryCommunity‐acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in the western world. Genetic variability affecting the host response to infection may play a role in susceptibility and outcome in patients with CAP. Mannose‐binding lectin (MBL) and l‐ficolin (l‐FCN) are two important activators of the complement system and they can enhance phagocytosis by opsonization. In a prospective cohort of 505 Dutch patients with CAP and 227 control participants we studied whether polymorphisms in the MBL (MBL2) and FCN (FCN2) genes influenced susceptibility and outcome. No difference in frequency of these genotypes was found between patients with CAP in general and controls. However, the +6424G>T single nucleotide polymorphism (SNP) in FCN2 was more common in patients with a Coxiella burnetii pneumonia (P = 0·014). Moreover, the haplotypes coding for the highest MBL serum levels (YA/YA and YA/XA) predisposed to atypical pneumonia (C. burnetii, Legionella or Chlamydia species or Mycoplasma pneumoniae) compared with controls (P = 0·016). Furthermore, patients with these haplotypes were more often bacteraemic (P = 0·019). It can therefore be concluded that MBL2 and FCN2 polymorphisms are not major risk factors for CAP in general, but that the +6424G>T SNP in the FCN2 gene predisposes to C. burnetii pneumonia. In addition, patients with genotypes corresponding with high serum MBL levels are at risk for atypical pneumonia, possibly caused by enhanced phagocytosis, thereby promoting cell entry of these intracellular bacteria.

show abstract

L-Ficolin Specifically Binds to Lipoteichoic Acid, a Cell Wall Constituent of Gram-Positive Bacteria, and Activates the Lectin Pathway of Complement

Cited by 232 publications

References 31 publications

Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

Trivalent Recognition Unit of Innate Immunity System

Mannose‐binding lectin and l‐ficolin polymorphisms in patients with community‐acquired pneumonia caused by intracellular pathogens

Contact Info

Product

Resources

About