RESUMEN
BACKGROUND: There has been an interest in the relationship between ABO blood groups and infertility. Many studies have investigated the association of ABO blood groups with diminished ovarian reserve (DOR), ovarian hyperstimulation syndrome (OHSS), and outcomes of assisted reproductive technology (ART), with controversial results. METHODS: A systematic review and meta-analysis was conducted to evaluating the association of ABO blood groups with DOR, OHSS, and outcomes of ART. RESULTS: Thirteen studies performed between 2010 and 2018 were included in this meta-analysis. DOR, OHSS, live birth rate (LBR), clinical pregnancy rate (CPR), miscarriage rate (MR) were reported in 9, 2, 4, 3, 2 studies, respectively. The combined results showed similar risk of DOR among individuals with blood group A (RR, 0.98; 95% confidence interval [CI], 0.85, 1.13), B (RR, 0.96; 95% CI, 0.76, 1.20), AB (RR, 1.00; 95% CI, 0.76, 1.30), and non-O (RR, 0.94; 95% CI, 0.79, 1.11) as compared to those with blood group O. Meta-analysis showed that the incidences of OHSS were similar in women with blood group A (RR, 1.05; 95% CI, 0.66, 1.66), B (RR, 1.04; 95% CI, 0.46, 2.35), AB (RR, 0.51; 95% CI, 0.10, 2.56), non-O (RR, 1.02; 95% CI, 0.65, 1.57) with blood group O. As to the clinical outcomes, meta-analysis showed no difference in LBR among individuals with blood group A (RR, 1.27; 95% CI, 0.74, 2.17), B (RR, 1.47; 95% CI, 0.95, 2.29), AB (RR, 1.48; 95% CI, 0.76, 2.90), non-O (RR, 1.28; 95% CI, 0.83, 1.98) when compared to those with blood group O. Similarly, the results also found that there were no difference in CPR and MR between women with blood A (CPR: RR, 1.12), B (CPR: RR, 1.08), AB (CPR: RR, 1.05), non-O (CPR: RR, 1.05; MR: RR, 0.94) and blood group O. CONCLUSIONS: ABO blood groups may not be associated with DOR, OHSS, LBR, CPR, and MR of ART. Infertility and ART outcomes are influenced by multiple factors. Blood groups should not be taken into account excessively during diagnosis and treatment of infertile women.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/fisiología , Reserva Ovárica/fisiología , Técnicas Reproductivas Asistidas , Adulto , Antígenos de Grupos Sanguíneos/fisiología , Femenino , Humanos , Infertilidad Femenina/sangre , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/epidemiología , Infertilidad Femenina/terapia , Embarazo , Resultado del Embarazo/epidemiología , Índice de Embarazo , Resultado del TratamientoRESUMEN
Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Histo-Blood Groups Antigens (HBGAs) have been described as attachment factors, promoting HuNoV infection. However, their role has not yet been elucidated. This study aims to evaluate the ability of HBGAs to protect HuNoVs against various factors naturally found in the human digestive system. The effects of acid pH and proteolytic enzymes (pepsin, trypsin, and chymotrypsin) on GII.4 virus-like particles (VLPs) and GII.4 HuNoVs were studied, both during interactions and non-interaction with HBGAs. The results showed that GII.4 VLPs and GII.4 HuNoVs behaved differently following the treatments. GII.4 VLPs were disrupted at a pH of less than 2.0 and in the presence of proteolytic enzymes (1,500 units/mL pepsin, 100 mg/mL trypsin, and 100 mg/mL chymotrypsin). VLPs were also partially damaged by lower concentrations of trypsin and chymotrypsin (0.1 mg/mL). Conversely, the capsids of GII.4 HuNoVs were not compromised by such treatments, since their genomes were not accessible to RNase. HBGAs were found to offer GII.4 VLPs no protection against an acid pH or proteolytic enzymes.
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Antígenos de Grupos Sanguíneos/metabolismo , Antígenos de Grupos Sanguíneos/fisiología , Infecciones por Caliciviridae/virología , Gastroenteritis/virología , Norovirus/efectos de los fármacos , Norovirus/patogenicidad , Péptido Hidrolasas/farmacología , Cápside/efectos de los fármacos , Quimotripsina/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Concentración de Iones de Hidrógeno , Norovirus/genética , Norovirus/metabolismo , Pepsina A/farmacología , Tripsina/farmacología , Acoplamiento Viral/efectos de los fármacosRESUMEN
BACKGROUND: Serological testing for extended RHCcEe, Kell, Kidd and Duffy blood grouping from multitransfused patients may not give correct blood grouping of the recipient. Hence molecular testing for these blood groups was compared with serological groups in a cohort of multitransfused thalassemia mjor and sickle cell anaemia patients. OBJECTIVE: Molecular genotyping of antigens of Rh (D, C, c, E, e), Kell (K, k), Duffy (Fya, Fyb) and Kidd (Jka, Jkb) blood group antigens by PCR and PCR-RFLP methods and comparison of predicted genotypes with their serological phenotypes. MATERIALS AND METHODS: A cohort of multitransfused thalassemia and sickle cell anemia patient were serologically and molecularly tested for RHCc, RHEe, K, k Fya, Fyb, Jka and Jkb antigens and compared. Serological testing was done by tube agglutination and molecular testing was done either by allele specific PCR or by RFLP technique just before next transfusion. RESULTS: In more than 80% of the cases recipient's molecular testing blood groups were at variance with serologically tested blood groups (pâ¯<â¯0.0001). Mixed field reactions in serological typing were common. In sickle cell anemia patients no discrepancy was found. Molecular technique results were checked by Sanger's sequencing. DISCUSSION: Extended phenotyping in multitransfused thalassemia patients by serological technique often donot detect the exact red cell phenotype of the recipient and molecular techniques for such grouping is preferable, especially in multitransfused thalassemia patients where red cells from previous transfusions continues to be present in significant numbers whenever the testing is done.
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Anemia de Células Falciformes/terapia , Antígenos de Grupos Sanguíneos/fisiología , Tipificación y Pruebas Cruzadas Sanguíneas/métodos , Talasemia beta/terapia , Anemia de Células Falciformes/sangre , Femenino , Genotipo , Humanos , Masculino , Talasemia beta/sangreRESUMEN
BACKGROUND: Due to the marked decline of maternal-fetal rhesus incompatibility, ABO alloimmunization has become the leading cause of the newborn hemolytic disease. It is estimated that 15-25 % of all pregnancies are concerned by ABO incompatibility. AIM: Neonatal blood group B seems to be more predisposing to acute hemolysis and severe hyperbilirubinemia. We propose to find if the newborn's blood group B represents a risk factor for severe hemolysis and/or severe hyperbilirubinemia. METHODS: We conducted a comparative study in the pediatrics department "B" of the Children Hospital of Tunis. We collected retrospectively the medical files of the newborn hospitalized for ABO alloimmunization (January 2011 - March 2014), then we compared two groups, OA group with OA alloimmunization and OB group with OB alloimmunization. A significant threshold was fixed to 0.05. RESULTS: We collected 98 cases of newborn ABO hemolytic disease. Both groups, OA and OB, were similar for the onset of jaundice, age of hospitalization, initial hemoglobin and indirect bilirubin levels. There were no statistically significant difference in the severity of hyperbilirubinemia and the use of exchange transfusion for the two groups. However, transfusion was statistically more frequent in the OB group compared to OA group (81.6 vs 10.2, p = 0,039, OR=2.9, 95% IC (1.1 - 7.8)). CONCLUSION: OB alloimmunization seems to induce more active hemolysis than OA one, with no difference for severe hyperbilirubinemia in both groups.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/fisiología , Incompatibilidad de Grupos Sanguíneos/epidemiología , Incompatibilidad de Grupos Sanguíneos/etiología , Eritroblastosis Fetal/epidemiología , Eritroblastosis Fetal/etiología , Sistema del Grupo Sanguíneo ABO/efectos adversos , Sistema del Grupo Sanguíneo ABO/inmunología , Antígenos de Grupos Sanguíneos/fisiología , Incompatibilidad de Grupos Sanguíneos/sangre , Eritroblastosis Fetal/sangre , Femenino , Humanos , Hiperbilirrubinemia Neonatal/epidemiología , Hiperbilirrubinemia Neonatal/etiología , Hiperbilirrubinemia Neonatal/inmunología , Recién Nacido , Enfermedades del Prematuro/sangre , Enfermedades del Prematuro/epidemiología , Masculino , Estudios Retrospectivos , Factores de Riesgo , Razón de MasculinidadRESUMEN
Blood type O is associated with a lower risk of myocardial infarction. Platelets play a critical role in myocardial infarction. It is not known whether the expression of blood group antigens on platelet proteins alters platelet function; we hypothesized that platelet function would be different between donors with blood type O and those with non-O. To address this hypothesis, we perfused blood from healthy type O donors (n = 33) or non-O donors (n = 54) over pooled plasma derived von Willebrand factor (VWF) protein and purified blood type-specific VWF at arterial shear and measured platelet translocation dynamics. We demonstrate for the first time that type O platelets travel farther at greater speeds before forming stable bonds with VWF. To further characterize these findings, we used a novel analytical model of platelet interaction. Modeling revealed that the kinetics for GPIb/VWF binding rate are significantly lower for type O compared with non-O platelets. Our results demonstrate that platelets from type O donors interact less with VWF at arterial shear than non-O platelets. Our results suggest a potential mechanism for the reduced risk of myocardial infarction associated with blood type O.
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Antígenos de Grupos Sanguíneos/fisiología , Plaquetas/fisiología , Adhesividad Plaquetaria , Agregación Plaquetaria , Complejo GPIb-IX de Glicoproteína Plaquetaria/metabolismo , Factor de von Willebrand/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Cinética , Masculino , Unión ProteicaRESUMEN
BACKGROUND The mechanism by which diabetes mellitus (DM) impacts the association between ABO blood types and pancreatic cancer is unclear. MATERIAL AND METHODS A retrospective case-control study of 264 patients with pancreatic cancer and 423 age- and sex-matched individuals with nonmalignant diseases was performed to assess whether ABO blood group and DM jointly contribute to pancreatic cancer risk. RESULTS A multivariate analysis with adjustments for risk factors revealed that blood type, chronic pancreatitis, and DM were significantly associated with increased pancreatic cancer risk. The estimated adjusted odds ratios (AORs with 95% confidence intervals [CIs]) were 2.130 (1.409-3.220) for blood type A, 2.383 (1.313-4.325) for blood type AB, 1.518 (1.012-2.276) for DM, and 10.930 (1.202-99.405) for chronic pancreatitis. Blood type A significantly modified the risk for pancreatic cancer in individuals with DM (AOR, 3.506; 95% CI, 1.659-7.409). CONCLUSIONS The risk for pancreatic cancer was associated with ABO blood type, DM, and chronic pancreatitis in a Chinese population. The risk was greatest for individuals with blood type A and DM.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/fisiología , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/etiología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Grupos Sanguíneos/fisiología , Tipificación y Pruebas Cruzadas Sanguíneas , Estudios de Casos y Controles , China , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Estudios Retrospectivos , Factores de RiesgoRESUMEN
More than 300 red blood cell (RBC) antigens belonging to 36 blood group systems have been officially reported in humans by the International Society of Blood Transfusion (ISBT). Phenotypic variability is directly linked to the expression of the 41 blood group genes. The Rh blood group system, which is composed of 54 antigens, is the most complex and polymorphic system. Many rare genetic variants within the RH (RHD and RHCE) genes, involving various mutational mechanisms (single-nucleotide substitutions, short insertions/deletions, rearrangements, large deletions), have been reported in the literature and reference databases. Expression of the variants induces variable clinical outcomes depending on their nature and impact on antigen structure. Their respective molecular and cellular effects remain however poorly studied. Biological resources to conduct this research are also barely available. We have paid a specific attention to three different classes of single-nucleotide substitutions: 1/ splice site variants in the Rh, Kell, Kidd, Junior and Langereis systems by the minigene splicing assay developed locally; 2/ missense variants in the RhD protein and their effect on intermolecular interaction with its protein partner RhAG, intracellular trafficking and plasma membrane integration; and 3/ synonymous variants in the RHD gene. Overall not only this project has fundamental objectives by analyzing the functional effect of variants in order to make genotype-phenotype correlation, but the aim is also to develop/engineer molecular tools and cell models to carry out those studies.
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Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/fisiología , Proteínas Sanguíneas/metabolismo , Regulación de la Expresión Génica , Estudios de Asociación Genética , Variación Genética , Humanos , Glicoproteínas de Membrana/metabolismo , Mutación Missense , Fenotipo , Mutación Puntual , Polimorfismo de Nucleótido Simple , Ingeniería de Proteínas , Mapeo de Interacción de Proteínas , Isoformas de Proteínas/genética , Sistema del Grupo Sanguíneo Rh-Hr/biosíntesis , Sistema del Grupo Sanguíneo Rh-Hr/genética , Sistema del Grupo Sanguíneo Rh-Hr/metabolismoRESUMEN
Human blood can be divided into groups, which is a method of blood classification based on the presence or absence of inherited erythrocyte surface antigens that can elicit immune response. According to the International Society of Blood Transfusion, there are 341 blood group antigens collected in 35 blood group systems. These antigens can be proteins, glycoproteins or glycosphingolipids, and function as transmembrane transporters, ion channels, adhesion molecules or receptors for other proteins. The majority of blood group antigens is present also on another types of cells. Due to their localization on the surface of cells, blood group antigens can act as receptors for various pathogens or their toxins, such as protozoa (malaria parasites), bacteria (Helicobacter pylori, Vibrio cholerae and Shigella dysenteriae) and viruses (Noroviruses, Parvoviruses, HIV). If the presence of group antigen (or its variant which arised due to mutation) is beneficial for the host (e.g. because pathogens are not able to bind to the cells), the blood group may become a selection trait, leading to its dissemination in the population exposed to that pathogen. There are thirteen blood group systems that can be related to pathogen resistance, and it seems that the particular influence was elicit by malaria parasites. It is generally thought that the high incidence of blood groups such as O in the Amazon region, Fy(a-b-) in Africa and Ge(-) in Papua-New Guinea is the result of selective pressure from malaria parasite. This review summarizes the data about relationship between blood groups and resistance to pathogens.
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Antígenos de Grupos Sanguíneos/clasificación , Antígenos de Grupos Sanguíneos/fisiología , Proteínas Sanguíneas/fisiología , Resistencia a la Enfermedad/fisiología , Malaria/inmunología , HumanosRESUMEN
The binding profiles of many human noroviruses (huNoVs) for human histo-blood group antigens have been characterized. However, quantitative-binding data for these important virus-host interactions are lacking. Here, we report on the intrinsic (per binding site) affinities of HBGA oligosaccharides for the huNoV VA387 virus-like particles (VLPs) and the associated subviral P particles measured using electrospray ionization mass spectrometry. The affinities of 13 HBGA oligosaccharides, containing A, B and H epitopes, with variable sizes (disaccharide to tetrasaccharide) and different precursor chain types (types 1, 2, 3, 5 and 6), were measured for the P particle, while the affinities of the A and B trisaccharides and A and B type 6 tetrasaccharides for the VLP were determined. The intrinsic affinities of the HBGA oligosaccharides for the P particle range from 500 to 2300 M(-1), while those of the A and B trisaccharides and the A and B type 6 tetrasaccharides for the VLP range from 1000 to 4000 M(-1). Comparison of these binding data with those measured previously for the corresponding P dimer reveals that the HBGA oligosaccharides tested exhibit similar intrinsic affinities for the P dimer and P particle. The intrinsic affinities for the VLP are consistently higher than those measured for the P particle, but within a factor of three. While the cause of the subtle differences in HBGA oligosaccharide affinities for the P dimer and P particle and those for the VLP remains unknown, the present data support the use of P dimers or P particles as surrogates to the VLP for huNoV-receptor-binding studies.
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Antígenos de Grupos Sanguíneos/química , Proteínas de la Cápside/química , Norovirus/inmunología , Antígenos de Grupos Sanguíneos/fisiología , Proteínas de la Cápside/inmunología , Humanos , Oligosacáridos/química , Unión Proteica , Virión/inmunologíaRESUMEN
We estimated the role of some endogenous factors influencing the effectiveness of ferrotherapy of iron-deficiency anemia. It was shown to yield good results in case of an initially low hemoglobin level, in the first half of menstrual cycle, in patients with normal Quetelet index or those with AB(IV) and B(III) blood groups at the age below 30 years.
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Anemia Ferropénica/terapia , Hierro/fisiología , Ciclo Menstrual/fisiología , Oligoelementos/deficiencia , Resultado del Tratamiento , Adulto , Anemia Ferropénica/sangre , Antígenos de Grupos Sanguíneos/fisiología , Femenino , Humanos , Hierro/administración & dosificación , Deficiencias de Hierro , Índice de Severidad de la Enfermedad , Oligoelementos/administración & dosificación , Adulto JovenRESUMEN
Histo-blood group antigens (HBGAs) have been suggested to be receptors or coreceptors for human noroviruses (HuNoVs) expressed on the intestinal epithelium. We isolated an enteric bacterium strain (SENG-6), closely related to Enterobacter cloacae, bearing HBGA-like substances from a fecal sample of a healthy individual by using a biopanning technique with anti-HBGA antibodies. The binding capacities of four genotypes of norovirus-like particles (NoVLPs) to Enterobacter sp. SENG-6 cells were confirmed by enzyme-linked immunosorbent assay (ELISA). Transmission electron microscopy demonstrated that NoVLPs bound mainly to extracellular polymeric substances (EPS) of Enterobacter sp. SENG-6, where the HBGA-like substances were localized. EPS that contained HBGA-like substances extracted from Enterobacter sp. SENG-6 was shown by enzyme-linked immunosorbent assay (ELISA) to be capable of binding to NoVLPs of a GI.1 wild-type strain (8fIIa) and a GII.6 strain that can recognize A antigen but not to an NoVLP GI.1 mutant strain (W375A) that loses the ability to bind to A antigen. Enzymatic cleavage of terminal N-acetyl-galactosamine residues in the bacterial EPS weakened bacterial EPS binding to the GI.1 wild-type strain (8fIIa). These results indicate that A-like substances in the bacterial EPS play a key role in binding to NoVLPs. Since the specific binding of HuNoVs to HBGA-positive enteric bacteria is likely to affect the transmission and infection processes of HuNoVs in their hosts and in the environment, further studies of human enteric bacteria and their binding capacity to HuNoVs will provide a new scientific platform for understanding interactions between two types of microbes that were previously regarded as biologically unrelated.
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Antígenos de Grupos Sanguíneos/fisiología , Enterobacteriaceae/inmunología , Enterobacteriaceae/virología , Norovirus/patogenicidad , Adsorción , Antígenos Bacterianos/genética , Antígenos Bacterianos/fisiología , Enterobacter/genética , Enterobacter/inmunología , Enterobacter/virología , Enterobacteriaceae/aislamiento & purificación , Espacio Extracelular/inmunología , Espacio Extracelular/virología , Heces/microbiología , Heces/virología , Humanos , Datos de Secuencia Molecular , Norovirus/inmunología , Norovirus/fisiología , Filogenia , ARN Bacteriano/genética , Virión/fisiología , Virión/ultraestructuraRESUMEN
The distal portion of rotavirus (RV) VP4 spike protein (VP8*) is implicated in binding to cellular receptors, thereby facilitating viral attachment and entry. While VP8* of some animal RVs engage sialic acid, human RVs often attach to and enter cells in a sialic acid-independent manner. A recent study demonstrated that the major human RVs (P[4], P[6], and P[8]) recognize human histo-blood group antigens (HBGAs). In this study, we performed a phylogenetic analysis of RVs and showed further variations of RV interaction with HBGAs. On the basis of the VP8* sequences, RVs are grouped into five P genogroups (P[I] to P[V]), of which P[I], P[IV], and P[V] mainly infect animals, P[II] infects humans, and P[III] infects both animals and humans. The sialic acid-dependent RVs (P[1], P[2], P[3], and P[7]) form a subcluster within P[I], while all three major P genotypes of human RVs (P[4], P[6], and P[8]) are clustered in P[II]. We then characterized three human RVs (P[9], P[14], and P[25]) in P[III] and observed a new pattern of binding to the type A antigen which is distinct from that of the P[II] RVs. The binding was demonstrated by hemagglutination and saliva binding assay using recombinant VP8* and native RVs. Homology modeling and mutagenesis study showed that the locations of the carbohydrate binding interfaces are shared with the sialic acid-dependent RVs, although different amino acids are involved. The P[III] VP8* proteins also bind the A antigens of the porcine and bovine mucins, suggesting the A antigen as a possible factor for cross-species transmission of RVs. Our study suggests that HBGAs play an important role in RV infection and evolution.
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Antígenos de Grupos Sanguíneos/fisiología , Proteínas de Unión al ARN/fisiología , Rotavirus/patogenicidad , Proteínas no Estructurales Virales/fisiología , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Sitios de Unión , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Proteínas de la Cápside/inmunología , Proteínas de la Cápside/fisiología , Bovinos , Especificidad del Huésped/fisiología , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Mucinas/metabolismo , Mutagénesis Sitio-Dirigida , Filogenia , Dominios y Motivos de Interacción de Proteínas , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/inmunología , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo , Rotavirus/clasificación , Rotavirus/genética , Rotavirus/fisiología , Infecciones por Rotavirus/inmunología , Infecciones por Rotavirus/transmisión , Infecciones por Rotavirus/virología , Ácidos Siálicos/metabolismo , Porcinos , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/inmunologíaAsunto(s)
Acuaporina 1/inmunología , Antígenos de Grupos Sanguíneos , Secuencia de Aminoácidos , Acuaporina 1/sangre , Acuaporina 1/química , Acuaporina 1/genética , Antígenos de Grupos Sanguíneos/química , Antígenos de Grupos Sanguíneos/clasificación , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/fisiología , Tipificación y Pruebas Cruzadas Sanguíneas , Permeabilidad de la Membrana Celular , Cromosomas Humanos Par 7/genética , Prueba de Coombs , Eritroblastosis Fetal/sangre , Eritroblastosis Fetal/genética , Femenino , Humanos , Inmunoglobulina G/inmunología , Recién Nacido , Isoanticuerpos/sangre , Masculino , Datos de Secuencia Molecular , Relación Estructura-Actividad , Agua/metabolismoAsunto(s)
Antígenos Bacterianos/inmunología , Antígenos de Grupos Sanguíneos/fisiología , Escherichia coli Enteropatógena/inmunología , Infecciones por Escherichia coli/inmunología , Galectina 4/fisiología , Galectinas/fisiología , Inmunidad Innata/fisiología , Animales , Antígenos de Grupos Sanguíneos/inmunología , Escherichia coli Enteropatógena/metabolismo , Escherichia coli Enteropatógena/patogenicidad , Galectina 3/inmunología , Galectina 3/fisiología , Galectina 4/inmunología , Galectinas/inmunología , Inmunidad Innata/inmunología , RatonesRESUMEN
The expression of ABO(H) blood group antigens causes deletion of cells that generate self-specific antibodies to these antigens but this deletion limits adaptive immunity toward pathogens bearing cognate blood group antigens. To explore potential defense mechanisms against such pathogens, given these limitations in adaptive immunity, we screened for innate proteins that could recognize human blood group antigens. Here we report that two innate immune lectins, galectin-4 (Gal-4) and Gal-8, which are expressed in the intestinal tract, recognize and kill human blood group antigen-expressing Escherichia coli while failing to alter the viability of other E. coli strains or other Gram-negative or Gram-positive organisms both in vitro and in vivo. The killing activity of both Gal-4 and Gal-8 is mediated by their C-terminal domains, occurs rapidly and independently of complement and is accompanied by disruption of membrane integrity. These results demonstrate that innate defense lectins can provide immunity against pathogens that express blood group-like antigens on their surface.
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Antígenos Bacterianos/inmunología , Antígenos de Grupos Sanguíneos/fisiología , Escherichia coli Enteropatógena/inmunología , Infecciones por Escherichia coli/inmunología , Galectina 4/fisiología , Galectinas/fisiología , Inmunidad Innata/fisiología , Animales , Antígenos de Grupos Sanguíneos/inmunología , Escherichia coli Enteropatógena/metabolismo , Escherichia coli Enteropatógena/patogenicidad , Epítopos , Citometría de Flujo , Galectina 3/inmunología , Galectina 3/fisiología , Galectina 4/inmunología , Galectinas/inmunología , Humanos , Inmunidad Innata/inmunología , Ratones , Estructura Terciaria de Proteína , Proteínas RecombinantesRESUMEN
Timely elimination of damaged mitochondria is essential to protect cells from the potential harm of disordered mitochondrial metabolism and release of proapoptotic proteins. In mammalian red blood cells, the expulsion of the nucleus followed by the removal of other organelles, such as mitochondria, are necessary differentiation steps. Mitochondrial sequestration by autophagosomes, followed by delivery to the lysosomal compartment for degradation (mitophagy), is a major mechanism of mitochondrial turnover. Here we show that mice lacking the essential autophagy gene Atg7 in the hematopoietic system develop severe anemia. Atg7(-/-) erythrocytes accumulate damaged mitochondria with altered membrane potential leading to cell death. We find that mitochondrial loss is initiated in the bone marrow at the Ter119(+)/CD71(High) stage. Proteomic analysis of erythrocyte ghosts suggests that in the absence of autophagy other cellular degradation mechanisms are induced. Importantly, neither the removal of endoplasmic reticulum nor ribosomes is affected by the lack of Atg7. Atg7 deficiency also led to severe lymphopenia as a result of mitochondrial damage followed by apoptosis in mature T lymphocytes. Ex vivo short-lived hematopoietic cells such as monocytes and dendritic cells were not affected by the loss of Atg7. In summary, we show that the selective removal of mitochondria by autophagy, but not other organelles, during erythropoeisis is essential and that this is a necessary developmental step in erythroid cells.
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Anemia/etiología , Autofagia/fisiología , Mitocondrias/fisiología , Animales , Autofagia/genética , Proteína 7 Relacionada con la Autofagia , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/fisiología , Médula Ósea/crecimiento & desarrollo , Médula Ósea/fisiología , Codón/genética , Células Eritroides/metabolismo , Células Madre Hematopoyéticas/enzimología , Células Madre Hematopoyéticas/fisiología , Integrasas/genética , Ratones , Ratones Noqueados , Proteínas Asociadas a Microtúbulos/deficiencia , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/fisiología , Proteínas Proto-Oncogénicas c-vav/deficiencia , Proteínas Proto-Oncogénicas c-vav/genética , Proteínas Proto-Oncogénicas c-vav/fisiología , Transcripción GenéticaAsunto(s)
Antígenos de Grupos Sanguíneos , Eritrocitos/fisiología , Antígenos de Grupos Sanguíneos/química , Antígenos de Grupos Sanguíneos/inmunología , Antígenos de Grupos Sanguíneos/fisiología , Proteínas Sanguíneas/química , Proteínas Sanguíneas/inmunología , Proteínas Sanguíneas/fisiología , Transfusión Sanguínea , Dióxido de Carbono/sangre , Envejecimiento Eritrocítico , Eritrocitos/inmunología , Eritrocitos Anormales , Enfermedades Hematológicas/sangre , Enfermedades Hematológicas/genética , Hemoglobinas/fisiología , Humanos , Isoantígenos/inmunología , Modelos Moleculares , Oxígeno/sangre , Conformación ProteicaRESUMEN
The special blood group antigen Mi.III exhibits a characteristic hybrid structure of glycophorin A (GPA) and glycophorin B, termed Gp.Mur. This phenotype has exceptionally high occurrence rates in several indigenous tribes in Taiwan ( approximately 21.2%-88.4%). Because glycophorin/Miltenberger begins interaction with anion exchanger-1 (AE1) in the endoplasmic reticulum, we hypothesized that the AE1-based macrocomplexes on erythrocyte membranes obtained from Mi.III(+) people could be differentiated from those obtained from non-Miltenberger people. Quantitative mass spectrometric comparison of the AE1-based complexes by iTRAQ (Applied Biosystems) revealed 25% to 67% higher expression of AE1 in Mi.III(+) erythrocytes. In accordance with the higher AE1 level, the Mi.III(+) erythrocytes exhibited superior HCO(3)(-) capacities, pH homeostasis, and osmotic resistance. Cotransfection experiments in HEK293 cells showed that Gp.Mur, like GPA, enhanced trafficking of AE1 to the plasma membrane. In summary, the increased surface expression of AE1 in Mi.III(+) erythrocytes could be attributed to the additive effect of GPA and Gp.Mur coexpression.
Asunto(s)
Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Antígenos de Grupos Sanguíneos/metabolismo , Antígenos de Grupos Sanguíneos/fisiología , Línea Celular/metabolismo , Retículo Endoplásmico/metabolismo , Eritrocitos/metabolismo , Citometría de Flujo/métodos , Glicoforinas/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Inmunoprecipitación , Modelos Biológicos , Ósmosis , Fenotipo , TransfecciónRESUMEN
In this novel study, we have for the first time identified evolutionarily conserved capsid residues in an individual chronically infected with norovirus (GGII.3). From 2000 to 2003, a total of 147 P1-1 and P2 capsid sequences were sequenced and investigated for evolutionarily conserved and functionally important residues by the evolutionary trace (ET) algorithm. The ET algorithm revealed more absolutely conserved residues (ACR) in the P1-1 domain (47/53, 88 %) as compared with the P2 domain (86/133, 64 %). The capsid P1-1 and P2 domains evolved in time-dependent manner, with a distinct break point observed between autumn/winter of year 2000 (isolates P1, P3 and P5) and spring to autumn of year 2001 (isolates P11, P13 and P15), which presumably coincided with a change of clinical symptoms. Furthermore, the ET analysis revealed a similar receptor-binding pattern as reported for Norwalk and VA387 strains, with the CS-4 and CS-5 patch (Norwalk strain) including residues 329 and 377 and residues 306 and 310, respectively, all being ACR in all partitions. Most interesting was that residues 343, 344, 345, 374, 390 and 391 of the proposed receptor A and B trisaccharide binding site (VA387 strain) within the P2 domain remained ACR in all partitions, presumably because there was no selective advantage to alter the histo blood group antigens (HBGA) receptor binding specificity. In conclusion, this study provides novel insights to the evolutionary process of norovirus during chronic infection.