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Pesquisa : D12.776.124.486.274.250.260 [Categoria DeCS]
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  1 / 1889 MEDLINE  
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[PMID]:28449969
[Au] Autor:Le Doare K; Faal A; Jaiteh M; Sarfo F; Taylor S; Warburton F; Humphries H; Birt J; Jarju S; Darboe S; Clarke E; Antonio M; Foster-Nyarko E; Heath PT; Gorringe A; Kampmann B
[Ad] Endereço:Centre for International Child Health, Imperial College London, Norfolk Place, London W2 1PG, UK,; Paediatric Infectious Diseases Research Group, St. George's University of London, Cranmer Terrace, London SW17 0TE, UK; Vaccines & Immunity Theme, MRC Unit The Gambia, Atlantic Road, Fajara, Gambia
[Ti] Título:Association between functional antibody against Group B Streptococcus and maternal and infant colonization in a Gambian cohort.
[So] Source:Vaccine;35(22):2970-2978, 2017 05 19.
[Is] ISSN:1873-2518
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Vertical transmission of Group B Streptococcus (GBS) is a prerequisite for early-onset disease and a consequence of maternal GBS colonization. Disease protection is associated with maternally-derived anti-GBS antibody. Using a novel antibody-mediated C3b/iC3b deposition flow cytometry assay which correlates with opsonic killing we developed a model to assess the impact of maternally-derived functional anti-GBS antibody on infant GBS colonization from birth to day 60-89 of life. METHODS: Rectovaginal swabs and cord blood (birth) and infant nasopharyngeal/rectal swabs (birth, day 6 and day 60-89) were obtained from 750 mother/infant pairs. Antibody-mediated C3b/iC3b deposition with cord and infant sera was measured by flow cytometry. RESULTS: We established that as maternally-derived anti-GBS functional antibody increases, infant colonization decreases at birth and up to three months of life, the critical time window for the development of GBS disease. Further, we observed a serotype (ST)-dependent threshold above which no infant was colonized at birth. Functional antibody above the upper 95th confidence interval for the geometric mean concentration was associated with absence of infant GBS colonization at birth for STII (p<0.001), STIII (p=0.01) and STV (p<0.001). Increased functional antibody was also associated with clearance of GBS between birth and day 60-89. CONCLUSIONS: Higher concentrations of maternally-derived antibody-mediated complement deposition are associated with a decreased risk of GBS colonization in infants up to day 60-89 of life. Our findings are of relevance to establish thresholds for protection following vaccination of pregnant women with future GBS vaccines.
[Mh] Termos MeSH primário: Anticorpos Antibacterianos/imunologia
Imunidade Materno-Adquirida
Transmissão Vertical de Doença Infecciosa
Infecções Estreptocócicas/imunologia
Streptococcus/crescimento & desenvolvimento
Streptococcus/imunologia
[Mh] Termos MeSH secundário: Adulto
Anticorpos Antibacterianos/sangue
Portador Sadio
Criança
Pré-Escolar
Estudos de Coortes
Complemento C3b/imunologia
Feminino
Sangue Fetal/imunologia
Citometria de Fluxo
Gâmbia/epidemiologia
Seres Humanos
Técnicas Imunológicas
Lactente
Recém-Nascido
Estudos Longitudinais
Mães
Nasofaringe/microbiologia
Proteínas Opsonizantes
Gravidez
Complicações Infecciosas na Gravidez/microbiologia
Infecções Estreptocócicas/epidemiologia
Infecções Estreptocócicas/transmissão
Streptococcus/classificação
Streptococcus/isolamento & purificação
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Bacterial); 0 (Opsonin Proteins); 80295-43-8 (Complement C3b)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


  2 / 1889 MEDLINE  
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[PMID]:28452748
[Au] Autor:Baud A; Aymé L; Gonnet F; Salard I; Gohon Y; Jolivet P; Brodolin K; Da Silva P; Giuliani A; Sclavi B; Chardot T; Mercère P; Roblin P; Daniel R
[Ad] Endereço:CNRS, UMR8587, Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement, 91025 Evry, France.
[Ti] Título:SOLEIL shining on the solution-state structure of biomacromolecules by synchrotron X-ray footprinting at the Metrology beamline.
[So] Source:J Synchrotron Radiat;24(Pt 3):576-585, 2017 05 01.
[Is] ISSN:1600-5775
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Synchrotron X-ray footprinting complements the techniques commonly used to define the structure of molecules such as crystallography, small-angle X-ray scattering and nuclear magnetic resonance. It is remarkably useful in probing the structure and interactions of proteins with lipids, nucleic acids or with other proteins in solution, often better reflecting the in vivo state dynamics. To date, most X-ray footprinting studies have been carried out at the National Synchrotron Light Source, USA, and at the European Synchrotron Radiation Facility in Grenoble, France. This work presents X-ray footprinting of biomolecules performed for the first time at the X-ray Metrology beamline at the SOLEIL synchrotron radiation source. The installation at this beamline of a stopped-flow apparatus for sample delivery, an irradiation capillary and an automatic sample collector enabled the X-ray footprinting study of the structure of the soluble protein factor H (FH) from the human complement system as well as of the lipid-associated hydrophobic protein S3 oleosin from plant seed. Mass spectrometry analysis showed that the structural integrity of both proteins was not affected by the short exposition to the oxygen radicals produced during the irradiation. Irradiated molecules were subsequently analysed using high-resolution mass spectrometry to identify and locate oxidized amino acids. Moreover, the analyses of FH in its free state and in complex with complement C3b protein have allowed us to create a map of reactive solvent-exposed residues on the surface of FH and to observe the changes in oxidation of FH residues upon C3b binding. Studies of the solvent accessibility of the S3 oleosin show that X-ray footprinting offers also a unique approach to studying the structure of proteins embedded within membranes or lipid bodies. All the biomolecular applications reported herein demonstrate that the Metrology beamline at SOLEIL can be successfully used for synchrotron X-ray footprinting of biomolecules.
[Mh] Termos MeSH primário: Complemento C3b/química
Síncrotrons
[Mh] Termos MeSH secundário: Seres Humanos
Estrutura Molecular
Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
80295-43-8 (Complement C3b)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171214
[Lr] Data última revisão:
171214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1107/S1600577517002478


  3 / 1889 MEDLINE  
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[PMID]:28843904
[Au] Autor:Sünderhauf A; Skibbe K; Preisker S; Ebbert K; Verschoor A; Karsten CM; Kemper C; Huber-Lang M; Basic M; Bleich A; Büning J; Fellermann K; Sina C; Derer S
[Ad] Endereço:Institute of Nutritional Medicine, Molecular Gastroenterology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
[Ti] Título:Regulation of epithelial cell expressed C3 in the intestine - Relevance for the pathophysiology of inflammatory bowel disease?
[So] Source:Mol Immunol;90:227-238, 2017 Oct.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The complement system not only plays a critical role in efficient detection and clearance of bacteria, but also in intestinal immune homeostasis as mice deficient for key complement components display enhanced intestinal inflammation upon experimental colitis. Because underlying molecular mechanisms for this observation are unclear, we investigated the crosstalk between intestinal epithelial cells (IEC), bacteria and the complement system in the course of chronic colitis. Surprisingly, mouse intestinal epithelial cell lines constitutively express high mRNA levels of complement component 3 (C3), Toll-like receptor 2 (Tlr2) and Tlr4. Stimulation of these cells with lipopolysaccharide (LPS), but not with flagellin, LD-muramyldipeptide or peptidoglycan, triggered increased C3 expression, secretion and activation. Stimulation of the C3aR on these cell lines with C3a resulted in an increase of LPS-triggered pro-inflammatory response. Tissue biopsies from C57BL/6J mice revealed higher expression of C3, Tlr1, Tlr2 and Tlr4 in colonic primary IECs (pIECs) compared to ileal pIECs, while in germ-free mice no differences in C3 protein expression was observed. In DSS-induced chronic colitis mouse models, C3 mRNA expression was upregulated in colonic biopsies and ileal pIECs with elevated C3 protein in the lamina propria, IECs and the mucus. Notably, increased C3b opsonization of mucosa-attached bacteria and decreased fecal full-length C3 protein was observed in DSS-treated compared to untreated mice. Of significant interest, non-inflamed and inflamed colonic biopsy samples from CD but not UC patients displayed exacerbated C3 expression compared to controls. These findings suggest that a novel TLR4-C3 axis could control the intestinal immune response during chronic colitis.
[Mh] Termos MeSH primário: Colite Ulcerativa/patologia
Complemento C3a/biossíntese
Complemento C3b/biossíntese
Células Epiteliais/metabolismo
Mucosa Intestinal/patologia
[Mh] Termos MeSH secundário: Animais
Bactérias/imunologia
Linhagem Celular
Colite Ulcerativa/induzido quimicamente
Complemento C3a/secreção
Complemento C3b/secreção
Sulfato de Dextrana/toxicidade
Seres Humanos
Inflamação/patologia
Mucosa Intestinal/imunologia
Lipopolissacarídeos/farmacologia
Camundongos
Camundongos Endogâmicos C57BL
Transdução de Sinais/imunologia
Receptor 1 Toll-Like/biossíntese
Receptor 2 Toll-Like/biossíntese
Receptor 4 Toll-Like/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipopolysaccharides); 0 (Tlr2 protein, mouse); 0 (Tlr4 protein, mouse); 0 (Toll-Like Receptor 1); 0 (Toll-Like Receptor 2); 0 (Toll-Like Receptor 4); 80295-42-7 (Complement C3a); 80295-43-8 (Complement C3b); 9042-14-2 (Dextran Sulfate)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170828
[St] Status:MEDLINE


  4 / 1889 MEDLINE  
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[PMID]:28801815
[Au] Autor:Qi J; Wang J; Chen J; Su J; Tang Y; Wu X; Ma X; Chen F; Ruan C; Zheng XL; Wu D; Han Y
[Ad] Endereço:The First Affiliated Hospital of Soochow University, Jiangsu Institute of Haematology, Suzhou, China.
[Ti] Título:Plasma levels of complement activation fragments C3b and sC5b-9 significantly increased in patients with thrombotic microangiopathy after allogeneic stem cell transplantation.
[So] Source:Ann Hematol;96(11):1849-1855, 2017 Nov.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Transplantation-associated thrombotic microangiopathy (TA-TMA) is an uncommon but severe complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). However, the mechanism is unclear. From 2011 to 2014, 20 patients with TA-TMA, 20 patients without, and 54 patients with various other complications, including veno occlusive disease (VOD), graft-versus-host disease (GVHD), and infection, were recruited in the study. Plasma vWF antigen (vWFAg), vWF activity (vWFAc), and ADAMTS13 activity were determined in these patients by ELISAs and FRETS-vWF73 assay, respectively. Plasma C3b, sC5b-9, and CH50 were also determined by ELISAs. Plasma levels of C3b were significantly increased in patients with either TA-TMA (p < 0.0001) or GVHD (p < 0.01). Plasma sC5b-9 and CH50 levels in patients with TA-TMA were also significantly increased (p < 0.001). Plasma ADAMTS13 activity was lower in patients with VOD, but normal with other complications. Both plasma vWFAg and vWFAc levels were not elevated in patients with TA-TMA or VOD compared with those of other groups. Complement activation likely via an alternative pathway (increased C3b, sC5b-9, and CH50) may play a role in the pathogenesis of TA-TMA. ADAMTS13 activity is reduced in VOD, but the ADAMTS13/vWF axis appears to be unaffected in patients with TA-TMA.
[Mh] Termos MeSH primário: Ativação do Complemento/fisiologia
Complemento C3b/metabolismo
Complexo de Ataque à Membrana do Sistema Complemento/metabolismo
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Microangiopatias Trombóticas/sangue
Microangiopatias Trombóticas/etiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Biomarcadores/sangue
Feminino
Doença Enxerto-Hospedeiro/sangue
Doença Enxerto-Hospedeiro/diagnóstico
Doença Enxerto-Hospedeiro/etiologia
Transplante de Células-Tronco Hematopoéticas/tendências
Seres Humanos
Masculino
Microangiopatias Trombóticas/diagnóstico
Transplante Homólogo/efeitos adversos
Transplante Homólogo/tendências
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Complement Membrane Attack Complex); 0 (SC5b-9 protein complex); 80295-43-8 (Complement C3b)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170813
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3092-9


  5 / 1889 MEDLINE  
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[PMID]:28757372
[Au] Autor:DiScipio RG; Schraufstatter IU
[Ad] Endereço:Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92122, United States. Electronic address: rdiscipio@ca.tpims.org.
[Ti] Título:Magnetic bead based assays for complement component C5.
[So] Source:J Immunol Methods;450:50-57, 2017 Nov.
[Is] ISSN:1872-7905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Two novel magnetic agarose bead based assays have been developed to measure complement component C5 interaction with C3b and the Factor I Modules (FIMs) of C7. One innovation was to couple C3b onto the magnetic agarose bead using the alternative pathway C3 convertase, which resulted in a linkage of the ligand by a covalent ester bond. A second innovation was to employ nickel ion charged N,N,N'-tris(carboxymethyl)ethylene-diamine-magnetic agarose to capture recombinantly prepared C7 FIMs that were expressed with an oligo-histidine linker followed by an acidic domain that provided a spacer enabling the C7 modules exposure to C5. Detection was brought about by peroxidase coupled to C5. Both assays exhibited adequate statistics suitable for screening. As examples of the utility of these new methods, we chose to examine influence of natural products on C5 interaction. Fucoidan and ß-glucans were observed to inhibit C3b-C5 interaction, and dextran sulfate was similarly active; however, rosmarinic acid had no measurable effect. In contrast only ß-glucans from two species of macrofungi were able to interfere with interaction of C5 with the FIMs of C7.
[Mh] Termos MeSH primário: Ativação do Complemento
Complemento C3b/imunologia
Complemento C5/imunologia
Complemento C7/imunologia
Técnicas Imunológicas
Magnetismo
[Mh] Termos MeSH secundário: Ativação do Complemento/efeitos dos fármacos
Convertases de Complemento C3-C5/metabolismo
Complemento C3b/metabolismo
Complemento C5/metabolismo
Complemento C7/metabolismo
Ensaio de Atividade Hemolítica de Complemento
Inativadores do Complemento/farmacologia
Sulfato de Dextrana/farmacologia
Hemólise
Seres Humanos
Ferro/química
Polissacarídeos/farmacologia
Ligação Proteica
Sefarose/química
beta-Glucanas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C5); 0 (Complement C7); 0 (Complement Inactivating Agents); 0 (Polysaccharides); 0 (beta-Glucans); 80295-43-8 (Complement C3b); 9012-36-6 (Sepharose); 9042-14-2 (Dextran Sulfate); 9072-19-9 (fucoidan); E1UOL152H7 (Iron); EC 3.4.21.- (Complement C3-C5 Convertases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE


  6 / 1889 MEDLINE  
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[PMID]:28715494
[Au] Autor:Ourradi K; Xu Y; de Seny D; Kirwan J; Blom A; Sharif M
[Ad] Endereço:School of Clinical Sciences, University of Bristol, Musculoskeletal Research Unit, Learning and Research Building, Southmead Hospital, Bristol, United Kingdom.
[Ti] Título:Development and validation of novel biomarker assays for osteoarthritis.
[So] Source:PLoS One;12(7):e0181334, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Osteoarthritis (OA) is the most common chronic joint disease usually diagnosed at relatively advanced stages when there is irreparable damage to the joint(s). Recently, we have identified two novel biomarkers C3f and V65 which appear to be OA-specific and therefore potential markers of early disease. We report the development of immunoassays for quantitative measure of these two novel biomarkers. METHOD: Monoclonal and polyclonal antibodies were generated by immunising mouse and rabbits respectively with peptide-carrier conjugates of C3f and V65. Affinity purified antibodies were used for immunoassays development and assays validated using serum from OA patients and controls. RESULTS: The ELISAs developed showed spiked recovery of up to 96% for C3f and V65 peptides depending on serum dilutions with a coefficient of variation (CV) <10%. The intra- and inter-assay CVs for C3f and V65 were 1.3-10.8% and 4.2-10.3% respectively. Both assays were insensitive for measurements of the peptides in patients and the use of different signal amplification systems did not increase assay sensitivity. CONCLUSION: We have developed two immunoassays for measurements of C3f and V65 peptides biomarkers discovered by our earlier proteomic study. These assays could detect the endogenous peptides in serum samples from patients and controls but lacked sensitivity for accurate measurements of the peptides in patients. Our study highlights the difficulties and challenges of validating biomarker from proteomic studies and demonstrates how to overcome some of the technical challenges associated with developing immunoassays for small peptides.
[Mh] Termos MeSH primário: Biomarcadores/sangue
Complemento C3b/análise
Ensaio de Imunoadsorção Enzimática/métodos
Osteoartrite/sangue
Fragmentos de Peptídeos/sangue
Vitronectina/sangue
[Mh] Termos MeSH secundário: Animais
Formação de Anticorpos
Western Blotting
Seres Humanos
Camundongos
Osteoartrite/diagnóstico
Osteoartrite/imunologia
Coelhos
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Biomarkers); 0 (Peptide Fragments); 0 (Vitronectin); 0 (complement C3f); 80295-43-8 (Complement C3b)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181334


  7 / 1889 MEDLINE  
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[PMID]:28671664
[Au] Autor:Xue X; Wu J; Ricklin D; Forneris F; Di Crescenzio P; Schmidt CQ; Granneman J; Sharp TH; Lambris JD; Gros P
[Ad] Endereço:Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
[Ti] Título:Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses.
[So] Source:Nat Struct Mol Biol;24(8):643-651, 2017 Aug.
[Is] ISSN:1545-9985
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of C3b remains unclear. We present a crystal structure of C3b in complex with FI and regulator factor H (FH; domains 1-4 with 19-20). FI binds C3b-FH between FH domains 2 and 3 and a reoriented C3b C-terminal domain and docks onto the first scissile bond, while stabilizing its catalytic domain for proteolytic activity. One cleavage in C3b does not affect its overall structure, whereas two cleavages unfold CUB and dislodge the thioester-containing domain (TED), affecting binding of regulators and thereby determining the number of cleavages. These data explain how FI generates late-stage opsonins iC3b or C3dg in a context-dependent manner, to react to foreign, danger or healthy self signals.
[Mh] Termos MeSH primário: Complemento C3b/química
Complemento C3b/metabolismo
Fator H do Complemento/química
Fator H do Complemento/metabolismo
Fator I do Complemento/química
Fator I do Complemento/metabolismo
[Mh] Termos MeSH secundário: Cristalografia por Raios X
Seres Humanos
Modelos Moleculares
Ligação Proteica
Conformação Proteica
Proteólise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
80295-43-8 (Complement C3b); 80295-65-4 (Complement Factor H); EC 3.4.21.45 (Complement Factor I)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170704
[St] Status:MEDLINE
[do] DOI:10.1038/nsmb.3427


  8 / 1889 MEDLINE  
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[PMID]:28652401
[Au] Autor:Bettoni S; Galbusera M; Gastoldi S; Donadelli R; Tentori C; Spartà G; Bresin E; Mele C; Alberti M; Tortajada A; Yebenes H; Remuzzi G; Noris M
[Ad] Endereço:IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò," 24020 Ranica Bergamo, Italy.
[Ti] Título:Interaction between Multimeric von Willebrand Factor and Complement: A Fresh Look to the Pathophysiology of Microvascular Thrombosis.
[So] Source:J Immunol;199(3):1021-1040, 2017 Aug 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:von Willebrand factor (VWF), a multimeric protein with a central role in hemostasis, has been shown to interact with complement components. However, results are contrasting and inconclusive. By studying 20 patients with congenital thrombotic thrombocytopenic purpura (cTTP) who cannot cleave VWF multimers because of genetic deficiency, we investigated the mechanism through which VWF modulates complement and its pathophysiological implications for human diseases. Using assays of ex vivo serum-induced C3 and C5b-9 deposits on endothelial cells, we documented that in cTTP, complement is activated via the alternative pathway (AP) on the cell surface. This abnormality was corrected by restoring ADAMTS13 activity in cTTP serum, which prevented VWF multimer accumulation on endothelial cells, or by an anti-VWF Ab. In mechanistic studies we found that VWF interacts with C3b through its three type A domains and initiates AP activation, although assembly of active C5 convertase and formation of the terminal complement products C5a and C5b-9 occur only on the VWF-A2 domain. Finally, we documented that in the condition of ADAMTS13 deficiency, VWF-mediated formation of terminal complement products, particularly C5a, alters the endothelial antithrombogenic properties and induces microvascular thrombosis in a perfusion system. Altogether, the results demonstrated that VWF provides a platform for the activation of the AP of complement, which profoundly alters the phenotype of microvascular endothelial cells. These findings link hemostasis-thrombosis with the AP of complement and open new therapeutic perspectives in cTTP and in general in thrombotic and inflammatory disorders associated with endothelium perturbation, VWF release, and complement activation.
[Mh] Termos MeSH primário: Complemento C3b/metabolismo
Via Alternativa do Complemento
Células Endoteliais/imunologia
Microvasos/patologia
Trombose/fisiopatologia
Fator de von Willebrand/metabolismo
[Mh] Termos MeSH secundário: Proteína ADAMTS13/sangue
Proteína ADAMTS13/deficiência
Proteína ADAMTS13/imunologia
Proteína ADAMTS13/metabolismo
Adolescente
Adulto
Criança
Pré-Escolar
Convertases de Complemento C3-C5/metabolismo
Complemento C3b/imunologia
Complemento C5a/imunologia
Complemento C5a/metabolismo
Complexo de Ataque à Membrana do Sistema Complemento/imunologia
Complexo de Ataque à Membrana do Sistema Complemento/metabolismo
Células Endoteliais/metabolismo
Células Endoteliais/patologia
Feminino
Seres Humanos
Recém-Nascido
Masculino
Microvasos/imunologia
Púrpura Trombocitopênica Trombótica/congênito
Púrpura Trombocitopênica Trombótica/imunologia
Púrpura Trombocitopênica Trombótica/fisiopatologia
Trombose/imunologia
Adulto Jovem
Fator de von Willebrand/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement Membrane Attack Complex); 0 (von Willebrand Factor); 80295-43-8 (Complement C3b); 80295-54-1 (Complement C5a); EC 3.4.21.- (Complement C3-C5 Convertases); EC 3.4.24.87 (ADAMTS13 Protein); EC 3.4.24.87 (ADAMTS13 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170628
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601121


  9 / 1889 MEDLINE  
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[PMID]:28641140
[Au] Autor:Abdelhafez MM; Shaw J; Sutter D; Schnider J; Banz Y; Jenni H; Voegelin E; Constantinescu MA; Rieben R
[Ad] Endereço:Department of Clinical Research, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. Electronic address: mai.abdelhafez@dkf.unibe.ch.
[Ti] Título:Effect of C1-INH on ischemia/reperfusion injury in a porcine limb ex vivo perfusion model.
[So] Source:Mol Immunol;88:116-124, 2017 Aug.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Revascularization of an amputated limb within 4-6h is essential to avoid extensive ischemia/reperfusion (I/R) injury leading to vascular leakage, edema and tissue necrosis. I/R injury is a pathological inflammatory condition that occurs during reperfusion of an organ or tissue after prolonged ischemia. It is characterized by a complex crosstalk between endothelial cell activation and the activation of plasma cascades. Vasculoprotective pharmacological intervention to prevent I/R injury might be an option to prolong the time window between limb amputation and successful replantation. We used C1-easterase inhibitor (C1-INH) in this study because of its known inhibitory effects on the activation of the complement, coagulation and kinin cascades. Forelimbs of 8 large white pigs were amputated, subjected to ischemia, and then reperfused with autologous whole blood. All limbs were exposed to 9h of cold ischemia at 4°C. After 2h of cold ischemia the limbs were either perfused with of C1-INH (1U/ml in hydroxyethyl starch, n=8) or hydroxyethyl starch alone (n=7). After completion of the 9-h ischemia period, all limbs were ex vivo perfused with heparinized autologous whole blood for 12h using a pediatric heart lung machine to simulate in vivo revascularization. Our results show that I/R injury in the control group led to a significant elevation of tissue deposition of IgG and IgM, complement C3b/c, C5b-9 and MBL. Also, activation of the kinin system was significantly increased, namely bradykinin in plasma, and expression of bradykinin receptors 1 and 2 in tissue. In addition, markers for endothelial integrity like expression of CD31, VE-cadherin and heparan sulfate proteoglycans were decreased in reperfused tissue. Limb I/R injury also led to activation of the coagulation cascade with a significant elevation of fibrin and thrombin deposition and increased fibrinogen-like protein-2 expression. C1-INH treated limbs showed much less activation of plasma cascades and better protection of endothelial integrity compared to the reperfused control limbs. In conclusion, the use of the cytoprotective drug C1-INH significantly reduced I/R injury by protecting the vascular endothelium as well as the muscle tissue from deposition of immunoglobulins, complement and fibrin.
[Mh] Termos MeSH primário: Cotos de Amputação/irrigação sanguínea
Cotos de Amputação/patologia
Proteína Inibidora do Complemento C1/uso terapêutico
Neovascularização Fisiológica/efeitos dos fármacos
Traumatismo por Reperfusão/prevenção & controle
[Mh] Termos MeSH secundário: Amputação
Animais
Bradicinina/sangue
Complemento C3b/imunologia
Complexo de Ataque à Membrana do Sistema Complemento/imunologia
Fibrina/metabolismo
Fibrinogênio/metabolismo
Derivados de Hidroxietil Amido/uso terapêutico
Imunoglobulina G/imunologia
Imunoglobulina M/imunologia
Receptores da Bradicinina/sangue
Traumatismo por Reperfusão/patologia
Suínos
Trombina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C1 Inhibitor Protein); 0 (Complement Membrane Attack Complex); 0 (Hydroxyethyl Starch Derivatives); 0 (Immunoglobulin G); 0 (Immunoglobulin M); 0 (Receptors, Bradykinin); 80295-43-8 (Complement C3b); 9001-31-4 (Fibrin); 9001-32-5 (Fibrinogen); EC 3.4.21.5 (Thrombin); S8TIM42R2W (Bradykinin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE


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[PMID]:28542608
[Au] Autor:Nakamura K; Kusama K; Bai R; Ishikawa S; Fukushima S; Suda Y; Imakawa K
[Ad] Endereço:Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Kasama, Ibaraki, Japan.
[Ti] Título:Increase in complement iC3b is associated with anti-inflammatory cytokine expression during late pregnancy in mice.
[So] Source:PLoS One;12(5):e0178442, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Immunological tolerance between fetal allograft and mother is crucial for pregnancy establishment and maintenance; however, these mechanisms particularly those during the latter part of pregnancy have not been definitively elucidated. The aim of this study was to examine the presence and potential function of innate immunity characteristic to the middle to late pregnancy. We first characterized up-regulated proteins in decidua from day 11 pregnant (P11) mice using 2D-PAGE, followed by MALDI-TOF/MS analysis. These analyses identified increased complement component 3 (C3) and its derivatives in P11 decidua. We then found that in the decidual tissues, C3 mRNA increased on P15 and remained high on P19. C3 is converted to C3b and then iC3b by complement component factor I (Cfi) and complement receptor 1-like protein (Crry), both of which were present in P19 placentas. In addition, iC3b proteins and its receptor CR3 (Cd11b/Cd18) in decidual and placental tissues increased toward the latter phase of pregnancy. Moreover, CR3 subunit CD11b protein was predominantly localized to spongiotrophoblast layer in the P19 placenta. Because iC3b is known to induce anti-inflammatory cytokine production, the analysis was extended to examine changes in pro- and anti-inflammatory cytokines, Il12, Il10, and Tgfb1. Il12 expression decreased in P15 and P19 placenta, while high mRNA expression of Il10 and Tgfb1 was found in P19 placental tissues. Furthermore, placental Il10 and Tgfb1 mRNAs were down-regulated when pregnant mice were treated with an anti-C3 antibody, detecting C3, C3b and iC3b. These results indicated that C3 derivatives, in particular, iC3b and its receptor CR3 were up-regulated at the fetal-maternal interface, and suggest that iC3b may regulate the placental expression of anti-inflammatory cytokines, IL10 and TGFB1, during the latter phase of pregnancy.
[Mh] Termos MeSH primário: Anti-Inflamatórios/metabolismo
Complemento C3b/metabolismo
Citocinas/metabolismo
Inflamação/metabolismo
[Mh] Termos MeSH secundário: Animais
Regulação para Baixo/fisiologia
Feminino
Masculino
Camundongos
Camundongos Endogâmicos ICR
Placenta/metabolismo
Gravidez
RNA Mensageiro/metabolismo
Receptores de Complemento 3b/metabolismo
Regulação para Cima/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Cytokines); 0 (RNA, Messenger); 0 (Receptors, Complement 3b); 80295-43-8 (Complement C3b)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178442



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