Mannose-binding lectin and maladies of the bowel and liver

Mannose-binding lectin (MBL) is a pattern-recognition molecule that binds to characteristic carbohydrate mo-tifs present on the surface of many different pathogens. MBL binding stimulates the immune system via the lectin pathway of complement activation. In certain clinical situations, often characterized by pre-existing immune compromise, MBL deficiency increases the risk of infec-tious and other disease-specific complications. Many of the key pathogenic processes inherent to common gastroenterological diseases, such as infection, immuno-logical damage, and carcinogenesis, have been linked to MBL. This editorial reviews the biology of MBL, outlines key disease associations to document the breadth of influence of MBL, and finally, highlights the relevance of MBL to both gastroenterological health and disease.

Mannose-binding Lectin Two Gene Polymorphisms and Tuberculosis Susceptibility in Chinese Population: A Meta-analysis

Numerous studies have been done to explore the association between mannose-binding lectin two （MBL2） gene polymorphisms and the risk of tuberculosis （TB）. However, the results are inconsistent. We performed a meta-aualysis to investigate whether polymorphisms in the MBL2 gene were associated with TB risk. Databases including PubMed, Medline, Chinese Biomedicine Database, China National Knowledge Infrastructure, Wanfang Database, and Weipu Database were searched to find relevant articles published up to 2 October, 2012. Odds ratio （OR） with 95% confidence interval （CI） was used to evaluate the strength of association. All statistical tests were performed by using Revman 5.1 software and STATA 11.0 software. Six case-control studies including 1106 cases and 1190 controls were accepted in the meta-analysis. The results indicated that individuals carrying the MBL2 codon 54 B allele may have an increased risk of TB as compared with AA homozygotes （BB＋AB vs. AA： OR=1.52, 95% CI： 1.22-1.88）, whereas MBL2 ＋4 P/Q was possibly not associated with TB susceptibility in Chinese population.

Mannose-binding lectin 2 rs11003123 polymorphism is associated with the development of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis in the Chinese population

BACKGROUND： Mannose-binding lectin 2 （MBL2） plays a key role in the host immune response, but whether it is associ- ated with hepatocellular carcinoma （HCC） is not dear. The present study aimed to identify the association between MBL2 gene polymorphisms and HCC in patients with hepatitis B virus （I-IBV）-related cirrhosis in the Chinese population.

Early expression of mannose-binding lectin 2 during Aspergillus fumigatus infection in human corneal epithelial cells

AIM: To evaluate the early expression of mannose-binding lectin 2(MBL2) in human corneal epithelial cells(HCECs) infected by Aspergillus fumigatus(AF).METHODS: HCECs cultured in vitro with AF antigens and sampled at 0, 0.5, 1, 2, 4, 6 and 8h. The expression of MBL2 m RNA was evaluated by semiquantitative reverse transcription-polymerase chain reaction(RT-PCR). The expression of MBL2 protein in supernatant fluid was shown by enzyme linked immunosorbent assay(ELISA). MBL2 protein in HCECs was detected by immunocytochemistry at 0 and 24 h.RESULTS: MBL2 m RNA and protein are expressed in normal HCECs. The expression of MBL2 m RNA and protein in supernatant fluid begin to increase after being stimulated with AF antigens. The most significantly peak of MBL2 m RNA is in 2h. The protein of MBL2 in supernatant fluid decrease gradually after 0.5h. The protein in HCECs expression increase after stimulation of24 h.· CONCLUSION: MBL2 receptor expressed in normal HCECs in vitro. The stimulation by AF antigens can increase the early expression of it.

Expressions and clinical significances of mannose-binding lectin(MBL) and MBL-associated serine protease 2(MASP-2) in patients with thyroid neoplasm

Objective： The aim of the study was to detect the levels of mannose-binding lectin （MBL）, MBL-associated serine protease 2 （MASP-2） and explore the clinical significances of them in patients with primary thyroid neoplasms. Methods： By using ELISA method, we detected the serum levels of MBL and MASP-2 in 26 patients with papillary thyroid carcinoma （PTC）, 30 patients with thyroid adenoma （TA） and 26 healthy people, respectively. Results： Serum MBL level was （565.23 ± 76.70） μg/L in PTCs higher than （324.267 ±24.74） μg/L in TAs, and （152.69± 16.95） IJg/L in healthy of controlling group. There was statistical significance between PTC and TA （P 〈 0.05）, however there was no difference between TA and healthy （P 〉 0.05）. Serum MASP-2 level was （726.153± 78.88） pg/L in PTCs higher than （379.266 ± 30.26） μg/L in TAs, and （203.846 ± 29.09） μg/L in healthy. Serum MASP-2 level was higher in PTCs than TAs, and the difference had statistical significance （P 〈 0.01）. But no difference was observed between in TAs and healthy. Conclusion： These findings might reflect inflammatory processes induced by defense mechanisms, in response to the development of the turnout. MBL may also be involved in the elimination of possible tumourigenic pathogens.

Dietary sugars inhibit biologic functions of the pattern recognition molecule, mannose-binding lectin

Mannose-binding lectin (MBL), a mammalian lectin, is a pattern recognition molecule of the innate immune system and recognizes carbo-hydrates that are exposed on pathogens. In this study, we observed that fructose down regu-lates MBL-mediated innate immune mechanisms against both influenza A virus (IAV) and Staphy-lococcus aureus. These mechanisms include the lectin complement pathway and coagulation enzyme-like activities on both pathogens. Fur-thermore, fructose also reduces MBL-mediated phagocytosis of S. aureus and IAV and MBL- mediated IAV infection to epithelial cells. In contrast, sucrose inhibits MBL-mediated im-mune mechanisms against S. aureus but not IAV. Together, our studies show that dietary sugars, in particular fructose, negatively regulate the innate immunity against viral and bacterial pathogens.

Mannose-binding lectin 2 gene polymorphisms and their association with tuberculosis in a Chinese population

Background:Immune-and inflammation-related genes(IIRGs)play an important role in the pathogenesis of tuberculosis(TB).However,the relationship between IIRG polymorphisms and TB risk remains unknown.In this study,the gene polymorphisms and their association with tuberculosis were determined in a Chinese population.Methods:We performed a case-control study involving 1016 patients with TB and 507 healthy controls of Han Chinese origin.Sixty-four single-nucleotide polymorphisms(SNPs)belonging to 18 IIRGs were genotyped by the PCR-MassArray assay,and the obtained data was analyzed withχ2-test,Bonferroni correction,and unconditional logistic regression analysis.Results:We observed significant differences in the allele frequency of LTA rs2229094*C(P=0.015),MBL2 rs2099902*C(P=0.001),MBL2 rs930507*G(P=0.004),MBL2 rs10824793*G(P=0.004),and IL12RB1 rs2305740*G(P=0.040)between the TB and healthy groups.Increased TB risk was identified in the rs930507 G/G genotype(Padjusted=0.027)under a codominant genetic model as well as in the rs2099902(C/T+C/C)vs T/T genotype(Padjusted=0.020),rs930507(C/G+G/G)vs C/C genotype(Padjusted=0.027),and rs10824793(G/A+G/G)vs A/A genotype(Padjusted=0.017)under a dominant genetic model after Bonferroni correction in the analysis of the overall TB group rather than the TB subgroups.Furthermore,the rs10824793_rs7916582*GT and rs10824793_rs7916582*GC haplotypes were significantly associated with increased TB risk(P=0.001,odds ratio[OR]=1.421,95%confidence interval[CI]:1.152-1.753;and P=0.018,OR=1.364,95%CI:1.055-1.765,respectively).Moreover,the rs10824793_rs7916582*AT/AT or rs10824793_rs7916582*GT/GT diplotype showed a protective(P=0.003,OR=0.530,95%CI:0.349-0.805)or harmful(P=0.009,OR=1.396,95%CI:1.087-1.793)effect against the development of TB.Conclusions:This study indicated that MBL2 polymorphisms,haplotypes,and diplotypes were associated with TB susceptibility in the Han Chinese population.Additionally,larger sample size studies are needed to further confirm these findings in the future.

Molecular Modeling and Docking of Mannose-binding Lectin from Lycoris radiata

Lycoris radiata mannose-binding lectin（LRL） is a protein which binds mannose residues specifically. The maturation peptide and three mannose-binding domains（residues 49-57, 80-88 and 113--121） of LRL were identified by sequence analysis. The 3D structure of LRL constructed by homology modeling shaped a flstular triangular prism. Three flanks of the prism are mainly composed of β-sheets and each flank has a mannose-binding domain. According to the docking and dynamics simulation, the bindings of residues 49--57 and 80--88 with mannose are more stable than that of residues 113--121 with it. The key residues for binding mannose are Gin80, Asp82, Ash84 and Tyr88. The study preliminarily analyzed the interaction sites and mechanism of LRL with mannoses, which could be useful for the study on insect-resistance and related drug discovery of LRL.

The clinical relevance of MBL2 gene polymorphism and sepsis

Objective:To detect the clinical relevance of mannose-binding lectin 2(MBL2) gene polymorphism and sepsis in Chinese lived in Hainan island.Methods: Blood samples from 57 patients with sepsis and 69 patients without sepsis were collected in the ICU of several large hospitals in Hainan province. Genomic DNA was extracted from whole blood and then PCR purification product was sequenced and typed by 3730 sequencing analyzer. The concentration of MBIL2 in serum was detected by ELISA.Results: We found that genotype and allele distributions in two groups were in accordance with the Hardy-Weinberg Equilibrium. The frequency of GA genotype was significantly higher than that in non-sepsis group(P=0.013). A allele frequency in sepsis group was also much higher than that in non-sepsis group(P=0.028).Logister regression analysis showed that the patients who carried A allele were more prone to get sepsis than G allele carrier(P=0.014, OR=2,550, 95%CI=1.207-5.386). The MBL2 level in serum of sepsis patients with genotype GG and GA was significantly lower than that in non-sepsis group(P<0.05). In sepsis group, the MBL2 serum level of patients with genotype GA was obviously lower than that in patients with genotype GG(P<0.05).Conclusions: The variation of rs 1800450 G→A increased the incidence of sepsis and decreased the level of MBL2 in serum.

Genetic variants of innate immune receptors and infections after liver transplantation

Infection is the leading cause of complication after liver transplantation, causing morbidity and mortality in the first months after surgery. Allograft rejection is mediated through adaptive immunological responses, and thus immunosuppressive therapy is necessary after transplantation. In this setting, the presence of genetic variants of innate immunity receptors may increase the risk of post-transplant infection, in comparison with patients carrying wild-type alleles. Numerous studies have investigated the role of genetic variants of innate immune receptors and the risk of complication after liver transplantation, but their results are discordant. Tolllike receptors and mannose-binding lectin are arguably the most important studied molecules; however, many other receptors could increase the risk of infection after transplantation. In this article, we review the published studies analyzing the impact of genetic variants in the innate immune system on the development of infectious complications after liver transplantation.

Interaction of Immune System Protein with PEGylated and Un-PEGylated Polymeric Nanoparticles

Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PLGA-COOH and PLGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DLS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PLGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PLGA-PEG-NH2 indicating conformational changes in the protein structure.

Bioinformatics analysis of interaction between MBL2 and MASPs family proteins

Objective:To predict and analyze the interaction between mannose-binding lectin 2(MBL2)protein and mannan-binding lectin-related serine proteases(MASPs)family proteins by bioinformatics.Methods:Homology modeling(Swiss-model)and fold recognition(Phyre 2)were used to construct the structure of MBL2 protein and MASPs family proteins,respectively.STRING database and ZDOCK 3.02 were used to predict and analyze the interaction between MBL2 and MASP1 and MASP2 proteins.Results:MBL2 had direct interaction with MASP1 and MASP2,and formed an interaction network with COLEEC11,COLEC10,FCN2,and C4B.The binding sites of MBL2 and MASP1 and MASP2 overlapped highly.MBL2 participated in the binding of MASP1 residues,and most of them(77%)were also involved in the binding of MASP2,suggesting that MBL2 interacted with the proteins of MASPs family through the same region.Conclusion:MBL2 and MASPs family proteins play an important role in the activation of the complement system and immune defense of the body.

Overexpression of OsJAC1, a Lectin Gene, Suppresses the Coleoptile and Stem Elongation in Rice

Lectin plays an Important role In defense signaling In plants, but its function In plant growth and development is not well known. Previously, we cloneds rice （Oryza sativa L.） gene OsJAC1 encoding s msnnose-blndlng Jscslln-relsted lectln, and found that OsJAC1 was Jssmonlc acid （JA） Inducible. Here we cloned the promoter of OsJAC1, and GUS activity was detected In young roots, coleoptlles, sheaths, leaves, nodes of stems, stems, rschlses, pistils, stsmens and lemmss of OsJAC1：：GUS trsnsgenlc rice, suggesting that OsJAC1 Is s constitutive expression gene In rice. Moreover, OsJAC1-overexpressed （Ubi：：OsJAC1） rice showed dwarfism with shorter coleptlles resulting from the failure of cell elongation of coleoptlles. In addition, compared with coleoptlles of wild-type plants, those of OsJAC1 overexpresslon rice were more sensitive to JA treatment. These data revealed that, besides Its roles in defense response, lectin plays an Important role in rice growth and development.