Mannose-binding lectin (MBL) is an important component of the innate immunity, and it is responsible not only for opsonization of micro-organisms, but also for efferocytosis. The aim of this study was to investigate whether MBL concentrations and lectin complement pathway activity are altered in non-pregnant women with previous adverse pregnancy outcomes. Patients were divided into four groups on the basis of their history of pregnancy complications, including control patients who had uncomplicated pregnancies and term deliveries (control, n = 33), and three groups of patients with a history of pregnancy complications, including preterm labour (n = 29), recurrent miscarriage (n = 19) or unexplained intrauterine foetal death (IUFD; n = 17). All women enrolled in the study had an interval of three to six months following their previous pregnancy, and they agreed to have a blood sample taken. We found significantly higher MBL concentrations and functional activity of the lectin complement pathway in healthy controls who had previous uneventful term pregnancies (1341 ng/mL; activity 100% (IQR: 62%-100%)), compared to women with the history of IUFD (684 ng/mL, P = .008; activity 8.5% (IQR: 0%-97.8%), P = .011), recurrent miscarriage (524 ng/mL, P = .022; activity 44% (IQR: 4%-83%), P = .011) or preterm labour (799 ng/mL, P = .022; activity 62.5% (IQR: 0%-83%), P = .003). Our results suggest that inadequate function of the complement lectin pathway is associated with a higher risk of preterm labour, recurrent miscarriage and unexplained intrauterine foetal death.

• Klíčová slova
• intrauterine foetal death, mannose-binding lectin, preterm labour, recurrent miscarriage,
• MeSH
• dospělí MeSH
• komplikace těhotenství krev   epidemiologie   MeSH
• lektin vázající mannosu krev   MeSH
• lektinová dráha komplementu imunologie   MeSH
• lidé MeSH
• přirozená imunita imunologie   MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• výsledek těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lektin vázající mannosu MeSH
• MBL2 protein, human MeSH Prohlížeč

BACKGROUND: Recurrent aphthous stomatitis is one of the most prevalent oral mucosal immunological diseases. A recent case-control study in the Egyptian population suggested that single nucleotide polymorphism Gly54Asp (rs1800450) of the mannose-binding lectin 2 gene might affect the mannose-binding lectin serum level and recurrent aphthous stomatitis development. The aim of this study was to determine the distribution of six functional mannose-binding lectin 2 gene polymorphisms and analyse their role in recurrent aphthous stomatitis susceptibility in the Czech population. METHODS: The study included 227 subjects; 137 healthy people and 90 patients with recurrent aphthous stomatitis. Six mannose-binding lectin 2 gene polymorphisms (rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, rs1800451) were analysed by the SNaPshot assay method, mannose-binding lectin serum levels were determined by enzyme-linked immunosorbent assay (ELISA) method in a subgroup of subjects (N = 87). RESULTS: No significant differences in mean of mannose-binding lectin serum levels between healthy controls and patients with recurrent aphthous stomatitis were observed (383 ng/ml ± 249 standard deviation (SD) vs. 316 ng/ml ± 177 SD in remission phase vs. 343 ng/ml ± 254 SD in active phase; p > 0.05), also the allele and genotype frequencies of the studied mannose-binding lectin 2 polymorphisms did not differ significantly between the two groups (p > 0.05, odds ratio (OR): 0.75-1.23). Moreover, the distribution of mannose-binding lectin 2 haplotypes and haplogenotypes was similar in the healthy subjects and patients with recurrent aphthous stomatitis (p > 0.05, OR: 0.75-1.23). CONCLUSIONS: This study did not confirm the previously reported association of the mannose-binding lectin 2 Gly54Asp gene variant and low mannose-binding lectin serum level as the risk factors for susceptibility to recurrent aphthous stomatitis. In addition, no significant relationships between mannose-binding lectin 2 functional haplotypes or haplogenotypes and recurrent aphthous stomatitis were observed.

• Klíčová slova
• MBL, haplogenotype, haplotype, polymorphism, recurrent aphthous stomatitis,
• MeSH
• aftózní stomatitida * genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus MeSH
• lektin vázající mannosu MeSH
• lidé MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• lektin vázající mannosu MeSH

The two-nucleotide deletion recently detected in the mannose-binding lectin 2 gene in purebred and crossbred domestic pigs was not found among 68 wild boars representing 4 populations from Europe and Asia. This suggests that the deletion is a result of breeding and/or genetic drift/bottle necks.

• MeSH
• frekvence genu MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus MeSH
• lektin vázající mannosu genetika   MeSH
• molekulární sekvence - údaje MeSH
• mutace INDEL MeSH
• sekvenční delece MeSH
• Sus scrofa genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Japonsko MeSH
• Rakousko MeSH
• Švédsko MeSH
• Názvy látek
• lektin vázající mannosu MeSH

Mannose-binding lectin (MBL) deficiency caused by the variability in the MBL2 gene is responsible for the susceptibility to and severity of various infectious and autoimmune diseases. A combination of six single nucleotide polymorphisms (SNPs) has a major impact on MBL levels in circulation. The aim of this study is to design and validate a sensitive and economical method for determining MBL2 haplogenotypes. The SNaPshot assay is designed and optimized to genotype six SNPs (rs1800451, rs1800450, rs5030737, rs7095891, rs7096206, rs11003125) and is validated by comparing results with Sanger sequencing. Additionally, an algorithm for online calculation of haplogenotype combinations from the determined genotypes is developed. Three hundred and twenty-eight DNA samples from healthy individuals from the Czech population are genotyped. Minor allele frequencies (MAFs) in the Czech population are in accordance with those present in the European population. The SNaPshot assay for MBL2 genotyping is a high-throughput, cost-effective technique that can be used in further genetic-association studies or in clinical practice. Moreover, a freely available online application for the calculation of haplogenotypes from SNPs is developed within the scope of this project.

• Klíčová slova
• Haplogenotype Calculator, SNaPshot assay, genotyping, haplogenotypes, mannose-binding lectin, mannose-binding lectin gene (MBL2), single nucleotide polymorphism,
• Publikační typ
• časopisecké články MeSH

Chronic inflammation has been implicated as the underlying mechanism responsible for the pathophysiology of preterm labour. Mannose-binding lectin (MBL) plays a central role in the innate immune response and is thus an important component of the first line of defense. The aim of this study was to investigate whether serum concentrations of MBL correlated with the incidence of preterm birth and low birthweight in a cohort of women with signs of threatened preterm birth. A cohort of 60 patients who presented with regular contractions and/or short cervix (group A) between 24 and 32 weeks of gestation and 20 healthy controls (group B) who had no pregnancy complications and delivered at term were recruited into a prospective study. The following outcomes were recorded: presence of preterm labour and birthweight in all patients. MBL and high sensitivity C-reactive protein levels were measured in all serum samples. The serum concentrations of MBL were significantly reduced in patients with threatened preterm labour (Group A), compared to the control Group B. Furthermore, infants born to Group A mothers with MBL deficiency (n = 13, MBL ≤100 ng/mL) had significantly lower birthweights, compared to those born to Group A women with normal MBL serum concentrations (P < .0001). Our small cohort study demonstrated a strong association between MBL deficiency and preterm delivery, and associated low birthweight. MBL deficiency could thus be considered an important risk factor for preterm birth.

• Klíčová slova
• complement, inflammation, reproductive immunology,
• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lektin vázající mannosu krev   nedostatek   MeSH
• lidé MeSH
• porodní hmotnost MeSH
• předčasná porodní činnost krev   MeSH
• předčasný porod krev   MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• vrozené poruchy metabolismu komplikace   epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• lektin vázající mannosu MeSH

The opportunistic Gram-negative bacterium Burkholderia cenocepacia causes lethal infections in cystic fibrosis patients. Multivalent mannoside derivatives were prepared as potential inhibitors of lectin BC2L-A, one of the virulence factors deployed by B. cenocepacia in the infection process. An (α1→2)-thio-linked mannobioside mimic bearing an azide functionalized aglycon was conjugated to different multivalent scaffolds such as propargylated calix[4]arenes, methyl gallate and pentaerythritol by azide-alkyne 1,3-dipolar cycloaddition. The interaction between the glycoclusters and the mannose binding BC2L-A lectin from B. cenocepacia was examined by isothermal microcalorimetry, surface plasmon resonance, inhibition of yeast agglutination and analytical ultracentrifugation.

• Klíčová slova
• Anti-adhesion therapy, Burkholderia cenocepacia, Click reaction, Glycoclusters, Mannose-binding lectin,
• MeSH
• aglutinační testy MeSH
• Burkholderia cenocepacia chemie   MeSH
• kalorimetrie metody   MeSH
• kvasinky účinky léků   MeSH
• lektin vázající mannosu chemie   metabolismus   farmakologie   MeSH
• ligandy MeSH
• mannosidy chemická syntéza   chemie   metabolismus   MeSH
• povrchová plasmonová rezonance MeSH
• techniky syntetické chemie MeSH
• ultracentrifugace metody   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lektin vázající mannosu MeSH
• ligandy MeSH
• mannosidy MeSH

Mannose-binding lectin (MBL), activating protein of the lectin pathway of the complement system, is an important component of the non-specific immune response. MBL2 gene polymorphisms, both in the coding and promoter regions, lead to low or deficient serum MBL levels. Low serum MBL levels were shown to be associated with serious infectious complications, mainly in patients in whom other non-specific immune system barriers were disturbed (granulocytopenia, cystic fibrosis). We have analysed two promoter (-550 and -221) and three exon (codons 52, 54 and 57) MBL2 polymorphisms in a total of 94 patients with common variable immunodeficiency (CVID) from two immunodeficiency centres. Low-producing genotypes were associated with the presence of bronchiectasis (P = 0.009), lung fibrosis (P = 0.037) and also with respiratory insufficiency (P = 0.029). We could not demonstrate any association of MBL deficiency with age at onset of clinical symptoms, age at diagnosis, the number of pneumonias before diagnosis or serum immunoglobulin (Ig)G, IgA and IgM levels before initiation of Ig treatment. No association with emphysema development was observed, such as with lung function test abnormalities. No effect of MBL2 genotypes on the presence of diarrhoea, granuloma formation, lymphadenopathy, splenomegaly, frequency of respiratory tract infection or the number of antibiotic courses of the patients was observed. Our study suggests that low MBL-producing genotypes predispose to bronchiectasis formation, and also fibrosis and respiratory insufficiency development, but have no effect on other complications in CVID patients.

• MeSH
• běžná variabilní imunodeficience komplikace   genetika   MeSH
• dítě MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• imunoglobuliny krev   MeSH
• lektin vázající mannosu krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• plicní nemoci genetika   MeSH
• polymorfismus genetický MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Německo MeSH
• Názvy látek
• imunoglobuliny MeSH
• lektin vázající mannosu MeSH
• MBL2 protein, human MeSH Prohlížeč

The purple pigmented bacterium Chromobacterium violaceum is a dominant component of tropical soil microbiota that can cause rare but fatal septicaemia in humans. Its sequenced genome provides insight into the abundant potential of this organism for biotechnological and pharmaceutical applications and allowed an ORF encoding a protein that is 60% identical to the fucose binding lectin (PA-IIL) from Pseudomonas aeruginosa and the mannose binding lectin (RS-IIL) from Ralstonia solanacearum to be identified. The lectin, CV-IIL, has recently been purified from C. violaceum [Zinger-Yosovich, K., Sudakevitz, D., Imberty, A., Garber, N. C., and Gilboa-Garber, N. (2006) Microbiology 152, 457-463] and has been confirmed to be a tetramer with subunit size of 11.86 kDa and a binding preference for fucose. We describe here the cloning of CV-IIL and its expression as a recombinant protein. A complete structure-function characterization has been made in an effort to analyze the specificity and affinity of CV-IIL for fucose and mannose. Crystal structures of CV-IIL complexes with monosaccharides have yielded the molecular basis of the specificity. Each monomer contains two close calcium cations that mediate the binding of the monosaccharides, which occurs in different orientations for fucose and mannose. The thermodynamics of binding has been analyzed by titration microcalorimetry, giving dissociation constants of 1.7 and 19 microM for alpha-methyl fucoside and alpha-methyl mannoside, respectively. Further analysis demonstrated a strongly favorable entropy term that is unusual in carbohydrate binding. A comparison with both PA-IIL and RS-IIL, which have binding preferences for fucose and mannose, respectively, yielded insights into the monosaccharide specificity of this important class of soluble bacterial lectins.

• MeSH
• bakteriální proteiny chemie   genetika   izolace a purifikace   metabolismus   MeSH
• Chromobacterium chemie   metabolismus   MeSH
• entropie MeSH
• fukosa metabolismus   MeSH
• krystalizace MeSH
• lektin vázající mannosu chemie   genetika   izolace a purifikace   metabolismus   MeSH
• lektiny chemie   genetika   izolace a purifikace   metabolismus   MeSH
• mannosa metabolismus   MeSH
• molekulární modely MeSH
• rekombinantní proteiny metabolismus   MeSH
• rozpustnost MeSH
• sekundární struktura proteinů MeSH
• senzitivita a specificita MeSH
• statická elektřina MeSH
• vápník chemie   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vodíková vazba MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• bakteriální proteiny MeSH
• fucose-binding lectin MeSH Prohlížeč
• fukosa MeSH
• lektin vázající mannosu MeSH
• lektiny MeSH
• mannosa MeSH
• rekombinantní proteiny MeSH
• vápník MeSH

Activation of the lectin pathway of the complement system, as demonstrated by elevated levels of mannan-binding lectin proteins (MBL), contributes to vascular pathology in type 1 diabetes (T1D). Vascular complications are greatest in T1D individuals with concomitant insulin resistance (IR), however, whether IR amplifies activiation of the lectin pathway in T1D is unknown. We pooled pretreatment data from two RCTs and performed a cross-sectional analysis on 46 T1D individuals. We employed estimated glucose disposal rate (eGDR), a validated IR surrogate with cut-points of: <5.1, 5.1-8.7, and > 8.7 mg/kg/min to determine IR status, with lower eGDR values conferring higher degrees of IR. Plasma levels of MBL-associated proteases (MASP-1, MASP-2, and MASP-3) and their regulatory protein MAp44 were compared among eGDR classifications. In a subset of 14 individuals, we assessed change in MASPs and MAp44 following improvement in IR. We found that MASP-1, MASP-2, MASP-3, and MAp44 levels increased in a stepwise fashion across eGDR thresholds with elevated MASPs and MAp44 levels conferring greater degrees of IR. In a subset of 14 patients, improvement in IR was associated with significant reductions in MASPs, but not MAp44, levels. In conclusion, IR in T1D amplifies levels of MASP-1/2/3 and their regulator MAp44, and improvement of IR normalizes MASP-1/2/3 levels. Given that elevated levels of these proteins contribute to vascular pathology, amplification of the lectin pathway of the complement system may offer mechanistic insight into the relationship between IR and vascular complications in T1D.

• Klíčová slova
• complement, insulin resistance, mannan-binding lectin-associated serine proteases, type 1 diabetes,
• MeSH
• diabetes mellitus 1. typu * MeSH
• inzulinová rezistence * MeSH
• komplement MeSH
• lektin vázající mannosu * MeSH
• lektiny metabolismus   MeSH
• lidé MeSH
• průřezové studie MeSH
• serinové proteasy asociované s proteinem vázajícím mannosu metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• komplement MeSH
• lektin vázající mannosu * MeSH
• lektiny MeSH
• serinové proteasy asociované s proteinem vázajícím mannosu MeSH

PURPOSE: dialysis-induced inflammatory response including leukocyte and complement activation is considered a significant cofactor of chronic morbidity in long-term hemodialysis (HD) patients. The aim of this study was to provide better insight into its molecular background. EXPERIMENTAL DESIGN: in 16 patients, basic biocompatibility markers, i.e. leukocyte counts and C5a levels, were monitored during HD on a polysulfone membrane. Proteins adsorbed to dialyzers were eluted and separated by 2-DE. Selected proteins were identified by MS; ficolin-2 plasma levels were assessed. Data are given as medians (quartile ranges). RESULTS: in total, 7.2 (34.7) mg proteins were retrieved from dialyzer eluates and were resolved into 217 protein spots. The proteins most enriched in eluates (and hence selectively adsorbed) were those involved in complement activation (C3c, ficolin-2, mannan-binding lectin serine proteases, properdin) and cell adhesion (actin, caldesmon, tropomyosin, vitronectin, vinculin). A significant decrease of plasma ficolin-2 (41% [4.7], p<0.001) was evidenced during one HD session, associated with leukopenia (r=0.73, p=0.001) and C5a production (r=-0.62, p=0.01) at 15 min. CONCLUSIONS AND CLINICAL RELEVANCE: ficolin-2 adsorption to polysulfone dialyzer initiates the lectin pathway of complement activation, mediates dialysis-induced leukopenia, and results in a significant depletion of ficolin-2, an essential component of innate immunity.

• MeSH
• adsorpce MeSH
• dialýza ledvin přístrojové vybavení   metody   MeSH
• fikoliny MeSH
• lektinová dráha komplementu * MeSH
• lektiny chemie   metabolismus   MeSH
• lidé MeSH
• membrány umělé MeSH
• polymery chemie   metabolismus   MeSH
• proteom analýza   MeSH
• stanovení celkové genové exprese * MeSH
• sulfony chemie   metabolismus   MeSH
• zánět imunologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lektiny MeSH
• membrány umělé MeSH
• polymery MeSH
• polysulfone P 1700 MeSH Prohlížeč
• proteom MeSH
• sulfony MeSH