RESUMO
Mannose binding lectin is a lectin instrumental in the innate immunity. It recognizes carbohydrate patterns found on the surface of a large number of pathogenic micro-organisms, activating the complement system. However, this protein seems to increase the tissue damage after ischemia. In this paper is reviewed some aspects of harmful role of the mannose binding lectin in ischemia/reperfusion injury.
Assuntos
Reestenose Coronária/etiologia , Lectina de Ligação a Manose/fisiologia , Traumatismo por Reperfusão/etiologia , Constrição Patológica/etiologia , Estenose Coronária/etiologia , HumanosRESUMO
Mannose binding lectin is a lectin instrumental in the innate immunity. It recognizes carbohydrate patterns found on the surface of a large number of pathogenic micro-organisms, activating the complement system. However, this protein seems to increase the tissue damage after ischemia. In this paper is reviewed some aspects of harmful role of the mannose binding lectin in ischemia/reperfusion injury.
Lectina de ligação à manose é uma lectina instrumental na imunidade inata. Ela reconhece padrões de hidratos de carbono encontrados na superfície de um grande número de microrganismos patogênicos, que ativam o sistema complemento. No entanto, esta proteína parece aumentar o dano tecidual após isquemia. Neste trabalho são revisados alguns aspectos do papel nocivo da lectina de ligação à manose na lesão de isquemia/reperfusão.
Assuntos
Humanos , Traumatismo por Reperfusão/etiologia , Reestenose Coronária/etiologia , Lectina de Ligação a Manose/fisiologia , Constrição Patológica/etiologia , Estenose Coronária/etiologiaRESUMO
To produce an infection Trypanosoma cruzi must evade lysis by the complement system. During early stages of infection, the lectin pathway plays an important role in host defense and can be activated by binding of mannan-binding lectin (MBL) to carbohydrates on the surface of pathogens. We hypothesized that MBL has a dual role during parasite-host cell interaction as lectin complement pathway activator and as binding molecule to invade the host cell. We used two polarized strains of T. cruzi, R4 (susceptible) and 860 (resistant) strains, to investigate the role of MBL in complement-mediated lysis. Interestingly R4, but not 860 metacyclic strain, markedly increases the invasion of host cells, suggesting that MBL drives the invasion process while the parasite deactivates the Lectin complement pathway.
Assuntos
Lectina de Ligação a Manose/fisiologia , Proteínas de Protozoários/fisiologia , Trypanosoma cruzi/fisiologia , Animais , Doença de Chagas/parasitologia , Chlorocebus aethiops , Ativação do Complemento , Via Alternativa do Complemento , Interações Hospedeiro-Parasita , Humanos , Imunidade Inata , Células VeroRESUMO
Vasoocclusive crisis (VOC) is the major cause of morbidity and mortality in sickle cell anemia (SCA), which is caused by the occlusion of blood vessels, followed by ischemia or infarct, resulting in progressive damage to organs. However, this clinical manifestation is variable, indicating that this process could be influenced by modifier genes. The gene MBL2 which codes for mannose-binding lectin (MBL) has been associated with modifications in the progression of infectious and inflammatory vascular diseases. The aim of this study was to determine the frequency of the polymorphisms of exon 1 (alleles A/O) and promoter region -221 (alleles Y/X) of MBL2 in children with SCA and to verify their association with VOC. The determination of the polymorphism of exon 1 and the promoter region of MBL2 was performed by SYBR GREEN((R)) and Taqman((R)) system, respectively. In the patients with SCA, the frequency of the genotype related to high production of MBL was 0.46 (YA/YA) and for intermediate/low production was 0.54 (YA/XA, XA/XA, YA/YO, XA/YO, YO/YO). The frequency of the genotypes and haplotypes of MBL2 in patients with SCA did not differ from control individuals. The populations were in Hardy-Weinberg equilibrium. The patients were divided into two groups. The groups were separated by the frequency of VOC, which was defined by the total of VOC episodes divided by the age of the children at the end of this study. Since, we choose a cut point in FVOC <1 (n=48) (which we considered of mild presentation of disease) and FVOC >or=1 (n=39) (higher severity). In children with SCA, the frequency of the genotypes of MBL2 of intermediate/low expression for MBL was associated with FVOC >or=1 (p=0.0188 OR=3.15 CI=1.19-8.50). The results suggest that MBL2 polymorphism at promoter and first exon of MBL2 associated with low serum levels and structural alterations of MBL could modify the phenotype of the child with SCA related to VOC.
Assuntos
Anemia Falciforme/complicações , Lectina de Ligação a Manose/genética , Doenças Vasculares/etiologia , Alelos , Anemia Falciforme/genética , Criança , Pré-Escolar , Éxons/genética , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos/genética , Humanos , Lactente , Infarto/etiologia , Infarto/genética , Isquemia/etiologia , Isquemia/genética , Masculino , Lectina de Ligação a Manose/fisiologia , Regiões Promotoras Genéticas/genética , Índice de Gravidade de Doença , Doenças Vasculares/genéticaAssuntos
Anemia Falciforme/complicações , Isquemia/etiologia , Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único , Infecções Respiratórias/complicações , Alelos , Anemia Falciforme/sangue , Anemia Falciforme/genética , Criança , Pré-Escolar , Éxons/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Lactente , Recém-Nascido , Isquemia/fisiopatologia , Masculino , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/deficiência , Lectina de Ligação a Manose/fisiologia , Recidiva , Infecções Respiratórias/sangueRESUMO
The coronary endothelial luminal membrane (CELM) glycocalyx has diverse molecules involved in blood flow signal transduction. Evidence suggests that some of these structures may be lectinic. To test this, we synthesized two monosaccharide polymers (Mon-Pols) made of Mannose (Man-Pol) or Galactose (Gal-Pol) covalently coupled to Dextran (70 kDa) and used them as lectin affinity probes. In situ intracoronary infusion of both polymers resulted in CELM-binding but only Man-Pol caused a reduction in flow-induced positive inotropism and dromotropism. To demonstrate that our lectinic probes could bind to CELM lectins, a representative CELM protein fraction was isolated via intracoronary infusion of a cationic silica colloid and either Mannose- or Galactose-binding lectins were purified from the CELM protein fraction using the corresponding Mon-Pol affinity chromatography resin. Resin-bound CELM proteins were eluted with the corresponding monosaccharide. 2D-SDS-PAGE (pH 4-7) revealed 9 Mannose- and approximately 100 Galactose-selective CELM lectins. In summary, the CELM glycocalyx contains Mannose- and Galactose-binding lectins that may be involved in translating coronary flow into a cardiac parenchymal response.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Vasos Coronários/fisiologia , Endotélio Vascular/fisiologia , Galectinas/fisiologia , Lectina de Ligação a Manose/fisiologia , Músculo Liso Vascular/fisiologia , Animais , Técnicas Biossensoriais , Glicocálix/fisiologia , Coração/efeitos dos fármacos , Coração/fisiologia , Humanos , Mamíferos , Contração Muscular/fisiologia , Relaxamento Muscular/fisiologia , Vasoconstrição/fisiologia , Vasodilatação/fisiologiaRESUMO
Susceptibility to systemic lupus erythematosus (SLE) is associated with genetic, hormonal, immunological, and environmental factors. Many genes have been related with the appearance of SLE, including several loci that code different complement components and their receptors. Some genetic deficiencies of complement molecules are strongly associated with SLE, probably because these deficiencies could cause decreased clearance of apoptotic cell material. As a consequence of the apoptotic material accumulation, high levels of autoantigens can be presented inappropriately to the immune system in an inflammatory context, resulting in an imbalance on the mechanisms of immunological tolerance, immune system activation, and autoantibody production. Recent studies proposed a role to the mannose-binding lectin (MBL) in the SLE physiopathogenesis. This protein activates the complement system, and the presence of several polymorphisms at the promoter and coding regions of the MBL-2 gene determines alterations at the plasma levels of MBL. Some of these polymorphisms have been associated with SLE susceptibility, as well as with clinical and laboratory typical features of this disease, cardiovascular events, and infections. Besides, it has been described that the presence of anti-MBL autoantibodies in sera of SLE patients can influence MBL plasma levels and its functional activity.
Assuntos
Lúpus Eritematoso Sistêmico/etiologia , Lectina de Ligação a Manose/fisiologia , Autoanticorpos/sangue , Proteínas do Sistema Complemento , Predisposição Genética para Doença/genética , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/imunologia , Polimorfismo Genético/genética , Fatores de RiscoRESUMO
La lectina de unión a la manosa (MBL) es una colectina que se sintetiza en el hígado y es secretada al torrente sanguíneo, la cual es capaz de unirse con estructuras repetidas de azúcares presentes en una amplia variedad de bacterias y otros microorganismos promoviendo su eliminación mediante la activación del complemento a través de serín proteasas asociadas. A las deficiencias de MBL se les considera como un importante factor de riesgo de infecciones en niños y en individuos inmunosuprimidos. Se discute la evidencia de que la MBL contribuye de forma importante a la inmunidad innata con el incremento de la susceptibilidad a determinadas enfermedades o la incidencia en el curso de estas. Estudios preliminares del empleo de terapias sustitutivas con MBL han arrojado resultados prometedores, los que deben ofrecer evidencias acerca del significado fisiológico de esta proteína
Assuntos
Humanos , Lectina de Ligação a Manose/fisiologia , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/química , Lectina de Ligação a Manose/uso terapêuticoRESUMO
Using RNA extracted from Zantedeschia aethiopica young leaves and primers designed according to the conservative regions of Araceae lectins, the full-length cDNA of Z. aethiopica agglutinin (ZAA) was cloned by rapid amplification of cDNA ends (RACE). The full-length cDNA of zaa was 871 bp and contained a 417 bp open reading frame (ORF) encoding a lectin precursor of 138 amino acids. Through comparative analysis of zaa gene and its deduced amino acid sequence with those of other Araceae species, it was found that zaa encoded a precursor lectin with signal peptide. Secondary and three-dimensional structure analyses showed that ZAA had many common characters of mannose-binding lectin superfamily and ZAA was a mannose-binding lectin with three mannose-binding sites. Southern blot analysis of the genomic DNA revealed that zaa belonged to a multi-copy gene family
Assuntos
Lectina de Ligação a Manose/fisiologia , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/química , Lectina de Ligação a Manose , Proteínas de Plantas/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/química , Genes de Plantas/fisiologia , Genes de Plantas/genética , Plantas Geneticamente Modificadas/fisiologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/química , Regulação da Expressão Gênica de Plantas/fisiologia , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
Using RNA extracted from Zantedeschia aethiopica young leaves and primers designed according to the conservative regions of Araceae lectins, the full-length cDNA of Z. aethiopica agglutinin (ZAA) was cloned by rapid amplification of cDNA ends (RACE). The full-length cDNA of zaa was 871 bp and contained a 417 bp open reading frame (ORF) encoding a lectin precursor of 138 amino acids. Through comparative analysis of zaa gene and its deduced amino acid sequence with those of other Araceae species, it was found that zaa encoded a precursor lectin with signal peptide. Secondary and three-dimensional structure analyses showed that ZAA had many common characters of mannose-binding lectin superfamily and ZAA was a mannose-binding lectin with three mannose-binding sites. Southern blot analysis of the genomic DNA revealed that zaa belonged to a multi-copy gene family