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[PMID]:28732131
[Au] Autor:Thurman JM; Frazer-Abel A; Holers VM
[Ad] Endereço:University of Colorado Denver, Aurora.
[Ti] Título:The Evolving Landscape for Complement Therapeutics in Rheumatic and Autoimmune Diseases.
[So] Source:Arthritis Rheumatol;69(11):2102-2113, 2017 Nov.
[Is] ISSN:2326-5205
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The complement system is increasingly understood to play major roles in the pathogenesis of human inflammatory and autoimmune diseases. Because of this situation, there are rapidly expanding commercial efforts to develop novel complement inhibitors and effector pathway-modulating drugs. This review provides insights into the evolving understanding of the complement system components, mechanisms of activation within and across the 3 pathways (classical, alternative, and lectin), how the pathways are normally controlled and then dysregulated in target tissues, and what diseases are known to be, in large part, complement-dependent through the successful development and approval of complement therapeutics in patients. Mechanisms of complement activation in rheumatoid arthritis, lupus, and thrombotic microangiopathies are also illustrated. In addition, the specific therapeutic drugs that are both approved and under development are discussed in the context of both nonrheumatic and rheumatic diseases. Finally, the methods by which the complement system can be assessed in humans through biomarker studies are outlined, with the goal of understanding, in specific patients, how the system is functioning.
[Mh] Termos MeSH primário: Doenças Autoimunes/tratamento farmacológico
Inativadores do Complemento/uso terapêutico
Doenças Reumáticas/tratamento farmacológico
[Mh] Termos MeSH secundário: Doenças Autoimunes/imunologia
Via Alternativa do Complemento/imunologia
Via Clássica do Complemento/imunologia
Lectina de Ligação a Manose da Via do Complemento/imunologia
Proteínas do Sistema Complemento/imunologia
Seres Humanos
Lúpus Eritematoso Sistêmico/tratamento farmacológico
Lúpus Eritematoso Sistêmico/imunologia
Terapia de Alvo Molecular
Doenças Reumáticas/imunologia
Microangiopatias Trombóticas/tratamento farmacológico
Microangiopatias Trombóticas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Complement Inactivating Agents); 9007-36-7 (Complement System Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1002/art.40219


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[PMID]:28724763
[Au] Autor:Kumar J; Yadav VN; Phulera S; Kamble A; Gautam AK; Panwar HS; Sahu A
[Ad] Endereço:Complement Biology Laboratory, National Centre for Cell Science, S. P. Pune University, Ganeshkhind, Pune, India.
[Ti] Título:Species Specificity of Vaccinia Virus Complement Control Protein for the Bovine Classical Pathway Is Governed Primarily by Direct Interaction of Its Acidic Residues with Factor I.
[So] Source:J Virol;91(19), 2017 Oct 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Poxviruses display species tropism-variola virus is a human-specific virus, while vaccinia virus causes repeated outbreaks in dairy cattle. Consistent with this, variola virus complement regulator SPICE (smallpox inhibitor of complement enzymes) exhibits selectivity in inhibiting the human alternative complement pathway and vaccinia virus complement regulator VCP (vaccinia virus complement control protein) displays selectivity in inhibiting the bovine alternative complement pathway. In the present study, we examined the species specificity of VCP and SPICE for the classical pathway (CP). We observed that VCP is ∼43-fold superior to SPICE in inhibiting bovine CP. Further, functional assays revealed that increased inhibitory activity of VCP for bovine CP is solely due to its enhanced cofactor activity, with no effect on decay of bovine CP C3-convertase. To probe the structural basis of this specificity, we utilized single- and multi-amino-acid substitution mutants wherein 1 or more of the 11 variant VCP residues were substituted in the SPICE template. Examination of these mutants for their ability to inhibit bovine CP revealed that E108, E120, and E144 are primarily responsible for imparting the specificity and contribute to the enhanced cofactor activity of VCP. Binding and functional assays suggested that these residues interact with bovine factor I but not with bovine C4(H O) (a moiety conformationally similar to C4b). Mapping of these residues onto the modeled structure of bovine C4b-VCP-bovine factor I supported the mutagenesis data. Taken together, our data help explain why the vaccine strain of vaccinia virus was able to gain a foothold in domesticated animals. Vaccinia virus was used for smallpox vaccination. The vaccine-derived virus is now circulating and causing outbreaks in dairy cattle in India and Brazil. However, the reason for this tropism is unknown. It is well recognized that the virus is susceptible to neutralization by the complement classical pathway (CP). Because the virus encodes a soluble complement regulator, VCP, we examined whether this protein displays selectivity in targeting bovine CP. Our data show that it does exhibit selectivity in inhibiting the bovine CP and that this is primarily determined by its amino acids E108, E120, and E144, which interact with bovine serine protease factor I to inactivate bovine C4b-one of the two subunits of CP C3-convertase. Of note, the variola complement regulator SPICE contains positively charged residues at these positions. Thus, these variant residues in VCP help enhance its potency against the bovine CP and thereby the fitness of the virus in cattle.
[Mh] Termos MeSH primário: Ativação do Complemento/imunologia
Via Alternativa do Complemento/imunologia
Via Clássica do Complemento/imunologia
Proteínas da Matriz Viral/imunologia
Proteínas Virais/imunologia
Tropismo Viral/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Bovinos
Proteína de Ligação ao Complemento C4b/imunologia
Fibrinogênio/metabolismo
Seres Humanos
Alinhamento de Sequência
Especificidade da Espécie
Vírus Vaccinia/imunologia
Vírus Vaccinia/patogenicidade
Proteínas da Matriz Viral/genética
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C4b-Binding Protein); 0 (SPICE protein, variola virus); 0 (Viral Matrix Proteins); 0 (Viral Proteins); 0 (complement-control protein, Vaccinia virus); 9001-32-5 (Fibrinogen)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE


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[PMID]:28663231
[Au] Autor:Nauser CL; Farrar CA; Sacks SH
[Ad] Endereço:Medical Research Council Centre for Transplantation, Division of Transplantation Immunology and Mucosal Biology, King's College London, National Health Service Guy's and St. Thomas' Trust, London, United Kingdom christopher.nauser@kcl.ac.uk.
[Ti] Título:Complement Recognition Pathways in Renal Transplantation.
[So] Source:J Am Soc Nephrol;28(9):2571-2578, 2017 Sep.
[Is] ISSN:1533-3450
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The complement system, consisting of soluble and cell membrane-bound components of the innate immune system, has defined roles in the pathophysiology of renal allograft rejection. Notably, the unavoidable ischemia-reperfusion injury inherent to transplantation is mediated through the terminal complement activation products C5a and C5b-9. Furthermore, biologically active fragments C3a and C5a, produced during complement activation, can modulate both antigen presentation and T cell priming, ultimately leading to allograft rejection. Earlier work identified renal tubule cell synthesis of C3, rather than hepatic synthesis of C3, as the primary source of C3 driving these effects. Recent efforts have focused on identifying the local triggers of complement activation. Collectin-11, a soluble C-type lectin expressed in renal tissue, has been implicated as an important trigger of complement activation in renal tissue. In particular, collectin-11 has been shown to engage L-fucose at sites of ischemic stress, activating the lectin complement pathway and directing the innate immune response to the distressed renal tubule. The interface between collectin-11 and L-fucose, in both the recipient and the allograft, is an attractive target for therapies intended to curtail renal inflammation in the acute phase.
[Mh] Termos MeSH primário: Proteínas do Sistema Complemento/imunologia
Rejeição de Enxerto/imunologia
Transplante de Rim
Lectinas/imunologia
Traumatismo por Reperfusão/imunologia
[Mh] Termos MeSH secundário: Imunidade Adaptativa
Animais
Colectinas/imunologia
Colectinas/metabolismo
Via Clássica do Complemento
Proteínas do Sistema Complemento/metabolismo
Seres Humanos
Lectinas/metabolismo
Lectina de Ligação a Manose/imunologia
Lectina de Ligação a Manose/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Collectins); 0 (Lectins); 0 (Mannose-Binding Lectin); 0 (collectin CL-K1, human); 9007-36-7 (Complement System Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170701
[St] Status:MEDLINE
[do] DOI:10.1681/ASN.2017010079


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[PMID]:28640789
[Au] Autor:Valenzuela NM; Thomas KA; Mulder A; Parry GC; Panicker S; Reed EF
[Ad] Endereço:1 UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA.2 Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.3 True North Therapeutics Inc., South San Francisco, CA.
[Ti] Título:Complement-Mediated Enhancement of Monocyte Adhesion to Endothelial Cells by HLA Antibodies, and Blockade by a Specific Inhibitor of the Classical Complement Cascade, TNT003.
[So] Source:Transplantation;101(7):1559-1572, 2017 Jul.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Antibody-mediated rejection (AMR) of most solid organs is characterized by evidence of complement activation and/or intragraft macrophages (C4d + and CD68+ biopsies). We previously demonstrated that crosslinking of HLA I by antibodies triggered endothelial activation and monocyte adhesion. We hypothesized that activation of the classical complement pathway at the endothelial cell surface by HLA antibodies would enhance monocyte adhesion through soluble split product generation, in parallel with direct endothelial activation downstream of HLA signaling. METHODS: Primary human aortic endothelial cells (HAEC) were stimulated with HLA class I antibodies in the presence of intact human serum complement. C3a and C5a generation, endothelial P-selectin expression, and adhesion of human primary and immortalized monocytes (Mono Mac 6) were measured. Alternatively, HAEC or monocytes were directly stimulated with purified C3a or C5a. Classical complement activation was inhibited by pretreatment of complement with an anti-C1s antibody (TNT003). RESULTS: Treatment of HAEC with HLA antibody and human complement increased the formation of C3a and C5a. Monocyte recruitment by human HLA antibodies was enhanced in the presence of intact human serum complement or purified C3a or C5a. Specific inhibition of the classical complement pathway using TNT003 or C1q-depleted serum significantly reduced adhesion of monocytes in the presence of human complement. CONCLUSIONS: Despite persistent endothelial viability in the presence of HLA antibodies and complement, upstream complement anaphylatoxin production exacerbates endothelial exocytosis and leukocyte recruitment. Upstream inhibition of classical complement may be therapeutic to dampen mononuclear cell recruitment and endothelial activation characteristic of microvascular inflammation during AMR.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/farmacologia
Adesão Celular/efeitos dos fármacos
Inativadores do Complemento/farmacologia
Via Clássica do Complemento/efeitos dos fármacos
Células Endoteliais/efeitos dos fármacos
Antígenos HLA-A/imunologia
Imunossupressores/farmacologia
Monócitos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Células Cultivadas
Técnicas de Cocultura
Complemento C3a/farmacologia
Complemento C5a/farmacologia
Relação Dose-Resposta a Droga
Células Endoteliais/imunologia
Células Endoteliais/metabolismo
Exocitose/efeitos dos fármacos
Antígenos HLA-A/metabolismo
Seres Humanos
Antígeno de Macrófago 1/imunologia
Antígeno de Macrófago 1/metabolismo
Monócitos/imunologia
Monócitos/metabolismo
Selectina-P/imunologia
Selectina-P/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Complement Inactivating Agents); 0 (HLA-A Antigens); 0 (Immunosuppressive Agents); 0 (Macrophage-1 Antigen); 0 (P-Selectin); 0 (SELP protein, human); 0 (TNT003); 80295-42-7 (Complement C3a); 80295-54-1 (Complement C5a)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001486


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[PMID]:28637898
[Au] Autor:Vogt LM; Talens S; Kwasniewicz E; Scavenius C; Struglics A; Enghild JJ; Saxne T; Blom AM
[Ad] Endereço:Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Skåne County Council, S-20502 Malmö, Sweden.
[Ti] Título:Activation of Complement by Pigment Epithelium-Derived Factor in Rheumatoid Arthritis.
[So] Source:J Immunol;199(3):1113-1121, 2017 Aug 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to identify molecules that trigger complement activation in rheumatic joints. C4d, the final cleavage product of C4 activation, is found in the diseased joint and can bind covalently to complement-activating molecules. By using a highly specific Ab against a cleavage neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium-derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas none were detected in SF from control subjects. Correlation analyses suggested that, in arthritis patients, C4d-PEDF complexes found in sera arise from the joints, as well as from other tissues, and levels of the complexes did not differ in sera of RA patients and healthy controls. When immobilized, recombinant PEDF expressed in eukaryotic cells activated the classical complement pathway but not the alternative or lectin pathways. C1q protein was demonstrated to bind immobilized PEDF, and PEDF was shown to bind to immobilized C1q, in particular its head regions, which are known to interact with other activators of the classical pathway. Our results call for further investigation into the role of PEDF in inflammatory processes in the joint, which, in combination with classical complement activation, appears to be part of a (patho-)physiologic response.
[Mh] Termos MeSH primário: Artrite Reumatoide/imunologia
Ativação do Complemento
Complemento C4/metabolismo
Proteínas do Olho/imunologia
Proteínas do Olho/metabolismo
Fatores de Crescimento Neural/imunologia
Fatores de Crescimento Neural/metabolismo
Serpinas/imunologia
Serpinas/metabolismo
Líquido Sinovial/química
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Artrite Reumatoide/fisiopatologia
Complemento C1q/metabolismo
Complemento C4/imunologia
Via Clássica do Complemento
Lectina de Ligação a Manose da Via do Complemento
Ensaio de Imunoadsorção Enzimática
Proteínas do Olho/sangue
Proteínas do Olho/genética
Feminino
Seres Humanos
Masculino
Meia-Idade
Fatores de Crescimento Neural/sangue
Fatores de Crescimento Neural/genética
Ligação Proteica
Serpinas/sangue
Serpinas/genética
Líquido Sinovial/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C4); 0 (Eye Proteins); 0 (Nerve Growth Factors); 0 (Serpins); 0 (pigment epithelium-derived factor); 80295-33-6 (Complement C1q)
[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:170623
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700018


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[PMID]:28601603
[Au] Autor:Wyatt SK; Witt T; Barbaro NM; Cohen-Gadol AA; Brewster AL
[Ad] Endereço:Department of Psychological Sciences, Purdue University, West Lafayette, IN, USA.
[Ti] Título:Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy.
[So] Source:Exp Neurol;295:184-193, 2017 Sep.
[Is] ISSN:1090-2430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Microglia-mediated neuroinflammation is widely associated with seizures and epilepsy. Although microglial cells are professional phagocytes, less is known about the status of this phenotype in epilepsy. Recent evidence supports that phagocytosis-associated molecules from the classical complement (C1q-C3) play novel roles in microglia-mediated synaptic pruning. Interestingly, in human and experimental epilepsy, altered mRNA levels of complement molecules were reported. Therefore, to identify a potential role for complement and microglia in the synaptodendritic pathology of epilepsy, we determined the protein levels of classical complement proteins (C1q-C3) along with other phagocytosis signaling molecules in human epilepsy. Cortical brain samples surgically resected from patients with refractory epilepsy (RE) and non-epileptic lesions (NE) were examined. Western blotting was used to determine the levels of phagocytosis signaling proteins such as the complements C1q and C3, MerTK, Trem2, and Pros1 along with cleaved-caspase 3. In addition, immunostaining was used to determine the distribution of C1q and co-localization to microglia and dendrites. We found that the RE samples had significantly increased protein levels of C1q (p=0.034) along with those of its downstream activation product iC3b (p=0.027), and decreased levels of Trem2 (p=0.045) and Pros1 (p=0.005) when compared to the NE group. Protein levels of cleaved-caspase 3 were not different between the groups (p=0.695). In parallel, we found C1q localization to microglia and dendrites in both NE and RE samples, and also observed substantial microglia-dendritic interactions in the RE tissue. These data suggest that aberrant phagocytic signaling occurs in human refractory epilepsy. It is likely that alteration of phagocytic pathways may contribute to unwanted elimination of cells/synapses and/or impaired clearance of dead cells. Future studies will investigate whether altered complement signaling contributes to the hyperexcitability that result in epilepsy.
[Mh] Termos MeSH primário: Ativação do Complemento/genética
Via Clássica do Complemento
Epilepsia/genética
Fagocitose/genética
[Mh] Termos MeSH secundário: Células Cultivadas
Córtex Cerebral/patologia
Complemento C1q/biossíntese
Complemento C1q/genética
Complemento C3/biossíntese
Complemento C3/genética
Via Clássica do Complemento/genética
Dendritos/genética
Dendritos/metabolismo
Epilepsia Resistente a Medicamentos/genética
Epilepsia Resistente a Medicamentos/patologia
Seres Humanos
Microglia/metabolismo
Proteína Quinase 1 Ativada por Mitógeno/biossíntese
Proteína Quinase 1 Ativada por Mitógeno/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C3); 80295-33-6 (Complement C1q); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
[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:170612
[St] Status:MEDLINE


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[PMID]:28582645
[Au] Autor:Yan J; Han D; Liu C; Gao Y; Li D; Liu Y; Yang G
[Ad] Endereço:Beijing Institute of Basic Medical Sciences, Beijing, China; State key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
[Ti] Título:Staphylococcus aureus VraX specifically inhibits the classical pathway of complement by binding to C1q.
[So] Source:Mol Immunol;88:38-44, 2017 Aug.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:VraX is a protein secreted by Staphylococcus aureus, an important human pathogen. A dramatic over expression of VraX is observed when S. aureus is exposed to several antimicrobial agents; however, its function remains unclear. Here, we aimed to reveal the function of this protein and the mechanism by which it affects the immune system to enhance the pathogenesis of the bacterium. Our results showed that VraX specifically inhibited the classical pathway of the complement system. In particular, VraX could bind to the C1q protein and block the formation of the C1 complex. Deletion of VraX decreased the pathogenesis of S. aureus. Our findings indicate that over expression of VraX might be a protective response for S. aureus survival.
[Mh] Termos MeSH primário: Ativação do Complemento/imunologia
Complemento C1q/imunologia
Via Clássica do Complemento/imunologia
Infecções Estafilocócicas/patologia
Staphylococcus aureus/patogenicidade
[Mh] Termos MeSH secundário: Animais
Ativação do Complemento/genética
Feminino
Deleção de Genes
Camundongos
Camundongos Endogâmicos BALB C
Ligação Proteica/imunologia
Coelhos
Infecções Estafilocócicas/genética
Infecções Estafilocócicas/imunologia
Infecções Estafilocócicas/microbiologia
Staphylococcus aureus/genética
Staphylococcus aureus/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
80295-33-6 (Complement C1q)
[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:170606
[St] Status:MEDLINE


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[PMID]:28512867
[Au] Autor:Woehl JL; Ramyar KX; Katz BB; Walker JK; Geisbrecht BV
[Ad] Endereço:Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas, 66506.
[Ti] Título:The structural basis for inhibition of the classical and lectin complement pathways by S. aureus extracellular adherence protein.
[So] Source:Protein Sci;26(8):1595-1608, 2017 Aug.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The extracellular adherence protein (Eap) plays a crucial role in pathogenesis and survival of Staphylococcus aureus by inhibiting the classical and lectin pathways of complement. We have previously shown that Eap binds with nanomolar affinity to complement C4b and disrupts the initial interaction between C4b and C2, thereby inhibiting formation of the classical and lectin pathway C3 pro-convertase. Although an underlying mechanism has been identified, the structural basis for Eap binding to C4b is poorly understood. Here, we show that Eap domains 3 and 4 each contain a low-affinity, but saturable binding site for C4b. Taking advantage of the high lysine content of Eap, we used a zero-length crosslinking approach to map the Eap binding site to both the α'- and γ-chains of C4b. We also probed the C4b/Eap interface through a chemical footprinting approach involving lysine modification, proteolytic digestion, and mass spectrometry. This identified seven lysines in Eap that undergo changes in solvent exposure upon C4b binding. We found that simultaneous mutation of these lysines to either alanine or glutamate diminished C4b binding and complement inhibition by Eap. Together, our results provide insight into Eap recognition of C4b, and suggest that the repeating domains that comprise Eap are capable of multiple ligand-binding modes.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Complemento C4b/química
Lisina/química
Proteínas de Ligação a RNA/química
Staphylococcus aureus/química
[Mh] Termos MeSH secundário: Alanina/química
Alanina/metabolismo
Sequência de Aminoácidos
Substituição de Aminoácidos
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Sítios de Ligação
Carbodi-Imidas/química
Complemento C4b/genética
Complemento C4b/metabolismo
Via Clássica do Complemento
Lectina de Ligação a Manose da Via do Complemento
Reagentes para Ligações Cruzadas/química
Cristalografia por Raios X
Expressão Gênica
Ácido Glutâmico/química
Ácido Glutâmico/metabolismo
Interações Hospedeiro-Patógeno
Seres Humanos
Lisina/metabolismo
Modelos Moleculares
Mutação
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Estrutura Secundária de Proteína
Proteínas de Ligação a RNA/genética
Proteínas de Ligação a RNA/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-ethyl-3-(3-(diethylamino)propyl)carbodiimide); 0 (Bacterial Proteins); 0 (Carbodiimides); 0 (Cross-Linking Reagents); 0 (Eap-N protein, Staphylococcus aureus); 0 (RNA-Binding Proteins); 0 (Recombinant Proteins); 3KX376GY7L (Glutamic Acid); 80295-50-7 (Complement C4b); K3Z4F929H6 (Lysine); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE
[do] DOI:10.1002/pro.3195


  9 / 1785 MEDLINE  
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[PMID]:28487087
[Au] Autor:van de Vosse E; van Ostaijen-Ten Dam MM; Vermaire R; Verhard EM; Waaijer JL; Bakker JA; Bernards ST; Eibel H; van Tol MJ; van Dissel JT; Haverkamp MH
[Ad] Endereço:Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: E.van_de_Vosse@lumc.nl.
[Ti] Título:Recurrent respiratory tract infections (RRTI) in the elderly: A late onset mild immunodeficiency?
[So] Source:Clin Immunol;180:111-119, 2017 Jul.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Elderly with late-onset recurrent respiratory tract infections (RRTI) often have specific anti-polysaccharide antibody deficiency (SPAD). We hypothesized that late-onset RRTI is caused by mild immunodeficiencies, such as SPAD, that remain hidden through adult life. We analyzed seventeen elderly RRTI patients and matched controls. We determined lymphocyte subsets, expression of BAFF receptors, serum immunoglobulins, complement pathways, Pneumovax-23 vaccination response and genetic variations in BAFFR and MBL2. Twelve patients (71%) and ten controls (59%) had SPAD. IgA was lower in patients than in controls, but other parameters did not differ. However, a high percentage of both patients (53%) and controls (65%) were MBL deficient, much more than in the general population. Often, MBL2 secretor genotypes did not match functional deficiency, suggesting that functional MBL deficiency can be an acquired condition. In conclusion, we found SPAD and MBL deficiency in many elderly, and conjecture that at least the latter arises with age.
[Mh] Termos MeSH primário: Envelhecimento/imunologia
Síndromes de Imunodeficiência/imunologia
Infecções Respiratórias/imunologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Envelhecimento/sangue
Envelhecimento/genética
Receptor do Fator Ativador de Células B/genética
Receptor do Fator Ativador de Células B/imunologia
Diferenciação Celular
Via Alternativa do Complemento
Via Clássica do Complemento
Proteínas do Sistema Complemento/análise
Feminino
Seres Humanos
Imunoglobulinas/sangue
Síndromes de Imunodeficiência/sangue
Síndromes de Imunodeficiência/genética
Linfócitos/citologia
Linfócitos/imunologia
Masculino
Lectina de Ligação a Manose/sangue
Lectina de Ligação a Manose/deficiência
Lectina de Ligação a Manose/genética
Lectina de Ligação a Manose/imunologia
Erros Inatos do Metabolismo/sangue
Erros Inatos do Metabolismo/genética
Erros Inatos do Metabolismo/imunologia
Meia-Idade
Vacinas Pneumocócicas/uso terapêutico
Recidiva
Infecções Respiratórias/sangue
Infecções Respiratórias/genética
Vacinação
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (23-valent pneumococcal capsular polysaccharide vaccine); 0 (B-Cell Activation Factor Receptor); 0 (Immunoglobulins); 0 (MBL2 protein, human); 0 (Mannose-Binding Lectin); 0 (Pneumococcal Vaccines); 0 (TNFRSF13C protein, human); 9007-36-7 (Complement System Proteins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE


  10 / 1785 MEDLINE  
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[PMID]:28301559
[Au] Autor:Rattan A; Pawar SD; Nawadkar R; Kulkarni N; Lal G; Mullick J; Sahu A
[Ad] Endereço:National Centre for Cell Science, S. P. Pune University Campus, Ganeshkhind, Pune, India.
[Ti] Título:Synergy between the classical and alternative pathways of complement is essential for conferring effective protection against the pandemic influenza A(H1N1) 2009 virus infection.
[So] Source:PLoS Pathog;13(3):e1006248, 2017 Mar.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The pandemic influenza A(H1N1) 2009 virus caused significant morbidity and mortality worldwide thus necessitating the need to understand the host factors that influence its control. Previously, the complement system has been shown to provide protection during the seasonal influenza virus infection, however, the role of individual complement pathways is not yet clear. Here, we have dissected the role of intact complement as well as of its individual activation pathways during the pandemic influenza virus infection using mouse strains deficient in various complement components. We show that the virus infection in C3-/- mice results in increased viral load and 100% mortality, which can be reversed by adoptive transfer of naïve wild-type (WT) splenocytes, purified splenic B cells, or passive transfer of immune sera from WT, but not C3-/- mice. Blocking of C3a and/or C5a receptor signaling in WT mice using receptor antagonists and use of C3aR-/- and C5aR-/- mice showed significant mortality after blocking/ablation of C3aR, with little or no effect after blocking/ablation of C5aR. Intriguingly, deficiency of C4 and FB in mice resulted in only partial mortality (24%-32%) suggesting a necessary cross-talk between the classical/lectin and alternative pathways for providing effective protection. In vitro virus neutralization experiments performed to probe the cross-talk between the various pathways indicated that activation of the classical and alternative pathways in concert, owing to coating of viral surface by antibodies, is needed for its efficient neutralization. Examination of the virus-specific complement-binding antibodies in virus positive subjects showed that their levels vary among individuals. Together these results indicate that cooperation between the classical and alternative pathways not only result in efficient direct neutralization of the pandemic influenza virus, but also lead to the optimum generation of C3a, which when sensed by the immune cells along with the antigen culminates in generation of effective protective immune responses.
[Mh] Termos MeSH primário: Via Alternativa do Complemento/imunologia
Via Clássica do Complemento/imunologia
Vírus da Influenza A Subtipo H1N1/imunologia
Infecções por Orthomyxoviridae/imunologia
[Mh] Termos MeSH secundário: Transferência Adotiva
Animais
Anticorpos Antivirais/imunologia
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
Feminino
Seres Humanos
Influenza Humana/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Camundongos Knockout
Testes de Neutralização
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006248



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