Studies of the binding of ficolin-2 and ficolin-3 from the complement lectin pathway to Leptospira biflexa, Pasteurella pneumotropica and Diarrheagenic Escherichia coli

Sahagún-Ruíz, Alfredo; Breda, Leandro Carvalho Dantas; Valencia, Mónica Marcela Castiblanco; Elias, Waldir P.; Munthe-Fog, Lea; Garred, Peter; Barbosa, Angela Silva; Isaac, Lourdes

doi:10.1016/j.imbio.2015.06.001

Cited by 13 publications

(15 citation statements)

References 64 publications

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“…Ficolins (Ficolin-1 or M-Ficolin, Ficolin-2 or L-Ficolin and Ficolin-3 or H-ficolin) are soluble molecules of the innate immune system that recognize a wide range of pathogen-associated molecular patterns (PAMPs) [7,8]. Ficolins form complexes with MASPs (MBL-associated serine proteases or MASPs) and activate complement through the lectin pathway, leading to opsonization and phagocytosis of pathogens, and stimulating the production of inflammatory cytokines and nitric oxide [9].…”

Section: Introductionmentioning

confidence: 99%

Association of a new FCN3 haplotype with high ficolin-3 levels in leprosy

et al. 2017

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Leprosy is a chronic inflammatory disease caused by Mycobacterium leprae that mainly affects the skin and peripheral nervous system, leading to a high disability rate and social stigma. Previous studies have shown a contribution of genes encoding products of the lectin pathway of complement in the modulation of the susceptibility to leprosy; however, the ficolin-3/FCN3 gene impact on leprosy is currently unknown. The aim of the present study was to investigate if FCN3 polymorphisms (rs532781899: g.1637delC, rs28362807: g.3524_3532insTATTTGGCC and rs4494157: g.4473C>A) and ficolin-3 serum levels play a role in the susceptibility to leprosy. We genotyped up to 190 leprosy patients (being 114 (60%) lepromatous), and up to 245 controls with sequence-specific PCR. We also measured protein levels using ELISA in 61 leprosy and 73 controls. FCN3 polymorphisms were not associated with disease, but ficolin-3 levels were higher in patients with FCN3 *2B1 (CinsA) haplotype (p = 0.032). Median concentration of ficolin-3 was higher in leprosy per se (26034 ng/mL, p = 0.005) and lepromatous patients (28295 ng/mL, p = 0.016) than controls (18231 ng/mL). In addition, high ficolin-3 levels (>33362 ng/mL) were more common in leprosy per se (34.4%) and in lepromatous patients (35.5%) than controls (19.2%; p = 0.045 and p = 0.047, respectively). Our results lead us to suggest that polymorphisms in the FCN3 gene cooperate to increase ficolin-3 concentration and that it might contribute to leprosy susceptibility by favoring M. leprae infection.

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Section: Introductionmentioning

confidence: 99%

Association of a new FCN3 haplotype with high ficolin-3 levels in leprosy

et al. 2017

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“…Ficolin-2 binds various clinically relevant pathogens including those affecting the respiratory system, whereas ficolin-3 does not (Hummelshøj et al 2012 ; Krarup et al 2005 ; Pan et al 2012 ). However, recently, it was shown that ficolin-3 binds enteropathogenic and enteropathoaggregative Escherichia coli (Sahagún-Ruiz et al 2015 ). Furthermore, the first evidence of antimicrobial activity of ficolin-3 was recently reported against the enteric commensal and opportunistic gut bacteria Hafnia alvei (Michalski et al 2015a ).…”

Section: Introductionmentioning

confidence: 99%

Frequency and distribution of FCN2 and FCN3 functional variants among MBL2 genotypes

2016

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The six types of pattern recognition molecules (PRMs) that initiate complement via the lectin pathway (LP) comprise collectins and ficolins. The importance of having various PRMs to initiate the LP is currently unclear. Mannan-binding lectin (MBL) is a collectin member of the LP PRMs. MBL deficiency is common with mild clinical consequence. Thus, the lack of MBL may be compensated for by the other PRMs. We hypothesized that variants FCN2 + 6424 and FCN3 + 1637delC that cause gene-dose-dependent reduction in ficolin-2 and ficolin-3 levels, respectively, may be rare in MBL-deficient individuals due to the importance of compensation within the LP. The aim of this study was to investigate the distribution and frequency of these variants among MBL2 genotypes in healthy subjects. The allele frequency of FCN2 + 6424 and FCN3 + 1637delC was 0.099 and 0.015, respectively, in the cohort (n = 498). The frequency of FCN2 + 6424 tended to be lower among MBL-deficient subjects (n = 53) than among MBL-sufficient subjects (n = 445) (0.047 versus 0.106, P = 0.057). In addition, individuals who were homozygous for FCN2 + 6424 were sufficient MBL producers. The frequency of FCN3 + 1637delC did not differ between the groups. The frequency of FCN2 + 6424 was similar in FCN3 + 1637delC carriers (n = 15) versus wild type (n = 498). Furthermore, subjects that were heterozygote carriers of both FCN2 + 6424 and FCN3 + 1637delC were sufficient MBL producers. In conclusion, FCN2 + 6424 carriers with MBL deficiency tend to be rare among healthy individuals. MBL-deficient individuals with additional LP PRM defects may be at risk to morbidity.

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“…Ficolins recognize a variety of ligands, including natural complex carbohydrates and monosaccharides; however, they exhibit some specificity towards N-acetylated non-sugar molecules [ 2 , 6 – 10 ]. A few reports described the binding of ficolins to bacteria [ 2 , 9 – 13 ], fungi [ 14 ], viruses [ 15 ], parasites [ 16 , 17 ] and eukaryotic cells [ 18 ]. Generally, ficolins differ in their ligand specificity.…”

Section: Introductionmentioning

confidence: 99%

“…coli (O111ab:H2 serotype) and enteroaggregative E . coli (O71 serotype) [ 13 ]. Ficolin-3 also binds surface antigens of late apoptotic cells [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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A New Ligand-Based Method for Purifying Active Human Plasma-Derived Ficolin-3 Complexes Supports the Phenomenon of Crosstalk between Pattern-Recognition Molecules and Immunoglobulins

et al. 2016

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Despite recombinant protein technology development, proteins isolated from natural sources remain important for structure and activity determination. Ficolins represent a class of proteins that are difficult to isolate. To date, three methods for purifying ficolin-3 from plasma/serum have been proposed, defined by most critical step: (i) hydroxyapatite absorption chromatography (ii) N-acetylated human serum albumin affinity chromatography and (iii) anti-ficolin-3 monoclonal antibody-based affinity chromatography. We present a new protocol for purifying ficolin-3 complexes from human plasma that is based on an exclusive ligand: the O-specific polysaccharide of Hafnia alvei PCM 1200 LPS (O-PS 1200). The protocol includes (i) poly(ethylene glycol) precipitation; (ii) yeast and l-fucose incubation, for depletion of mannose-binding lectin; (iii) affinity chromatography using O-PS 1200-Sepharose; (iv) size-exclusion chromatography. Application of this protocol yielded average 2.2 mg of ficolin-3 preparation free of mannose-binding lectin (MBL), ficolin-1 and -2 from 500 ml of plasma. The protein was complexed with MBL-associated serine proteases (MASPs) and was able to activate the complement in vitro. In-process monitoring of MBL, ficolins, and total protein content revealed the presence of difficult-to-remove immunoglobulin G, M and A, in some extent in agreement with recent findings suggesting crosstalk between IgG and ficolin-3. We demonstrated that recombinant ficolin-3 interacts with IgG and IgM in a concentration-dependent manner. Although this association does not appear to influence ficolin-3-ligand interactions in vitro, it may have numerous consequences in vivo. Thus our purification procedure provides Ig-ficolin-3/MASP complexes that might be useful for gaining further insight into the crosstalk and biological activity of ficolin-3.

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Studies of the binding of ficolin-2 and ficolin-3 from the complement lectin pathway to Leptospira biflexa, Pasteurella pneumotropica and Diarrheagenic Escherichia coli

Cited by 13 publications

References 64 publications

Association of a new FCN3 haplotype with high ficolin-3 levels in leprosy

Association of a new FCN3 haplotype with high ficolin-3 levels in leprosy

Frequency and distribution of FCN2 and FCN3 functional variants among MBL2 genotypes

A New Ligand-Based Method for Purifying Active Human Plasma-Derived Ficolin-3 Complexes Supports the Phenomenon of Crosstalk between Pattern-Recognition Molecules and Immunoglobulins

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