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[PMID]:28471021
[Au] Autor:Spessott WA; Sanmillan ML; Kulkarni VV; McCormick ME; Giraudo CG
[Ad] Endereço:Department of Pathology and Laboratory Medicine, University of Pennsylvania - The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
[Ti] Título:Syntaxin 4 mediates endosome recycling for lytic granule exocytosis in cytotoxic T-lymphocytes.
[So] Source:Traffic;18(7):442-452, 2017 Jul.
[Is] ISSN:1600-0854
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Adaptive and innate immunity utilize the perforin-killing pathway to eliminate virus-infected or cancer cells. Cytotoxic T-lymphocytes (CTLs) and natural killer cells mediate this process by releasing toxic proteins at the contact area with target cells known as immunological synapse (IS). Formation of a stable IS and exocytosis of toxic proteins requires persistent fusion of Rab11a recycling endosomes with the plasma membrane (PM) that may assure the delivery of key effector proteins. Despite the importance of the recycling endosomal compartment, the membrane fusion proteins that control this process at the IS remain elusive. Here, by performing knockdown experiments we found that syntaxin 4 (STX4) is necessary for cytotoxic activity and CD107a degranulation against target cells in a similar fashion to syntaxin 11, which is involved in lytic granule (LG) exocytosis and immunodeficiency when it is mutated. Using total internal reflection fluorescent microscopy we identified that STX4 mediates fusion of EGFP-Rab11a vesicles at the IS. Immunoprecipitation experiments in lysates of activated CTLs indicate that endogenous STX4 may drive this fusion step by interacting with cognate proteins: Munc18-3/SNAP23/VAMP7 and/or VAMP8. These results reveal the role of STX4 in mediating fusion of Rab11a endosomes upstream of lytic granules (LGs) exocytosis and further demonstrate the importance of this pathway in controlling CTL-mediated cytotoxicity.
[Mh] Termos MeSH primário: Grânulos Citoplasmáticos/metabolismo
Endossomos/metabolismo
Exocitose/imunologia
Proteínas Qa-SNARE/metabolismo
Linfócitos T Citotóxicos/metabolismo
[Mh] Termos MeSH secundário: Degranulação Celular
Linhagem Celular
Grânulos Citoplasmáticos/imunologia
Citotoxicidade Imunológica
Técnicas de Silenciamento de Genes
Seres Humanos
Proteína 1 de Membrana Associada ao Lisossomo/metabolismo
Transporte Proteico
Proteínas Qa-SNARE/genética
Linfócitos T Citotóxicos/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lysosomal-Associated Membrane Protein 1); 0 (Qa-SNARE Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1111/tra.12490


  2 / 543 MEDLINE  
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[PMID]:28456985
[Au] Autor:Andrews NW
[Ad] Endereço:Department of Cell Biology and Molecular Genetics, University of Maryland at College Park, 2134 Bioscience Research Building, College Park, MD, 20742-5815, USA. andrewsn@umd.edu.
[Ti] Título:Detection of Lysosomal Exocytosis by Surface Exposure of Lamp1 Luminal Epitopes.
[So] Source:Methods Mol Biol;1594:205-211, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Elevation in the cytosolic Ca concentration triggers exocytosis of lysosomes in many cell types. This chapter describes a method to detect lysosomal exocytosis in mammalian cells, which takes advantage of the presence of an abundant glycoprotein, Lamp1, on the membrane of lysosomes. Lamp1 is a transmembrane protein with a large, heavily glycosylated region that faces the lumen of lysosomes. When lysosomes fuse with the plasma membrane, epitopes present on the luminal domain of Lamp1 are exposed on the cell surface. The Lamp1 luminal epitopes can then be detected on the surface of live, unfixed cells using highly specific monoclonal antibodies and fluorescence microscopy. The main advantage of this method is its sensitivity, and the fact that it provides spatial information on lysosomal exocytosis at the single cell level.
[Mh] Termos MeSH primário: Lisossomos/metabolismo
[Mh] Termos MeSH secundário: Animais
Cálcio/metabolismo
Membrana Celular/metabolismo
Epitopos/análise
Exocitose/genética
Exocitose/fisiologia
Seres Humanos
Proteína 1 de Membrana Associada ao Lisossomo/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Epitopes); 0 (Lysosomal-Associated Membrane Protein 1); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6934-0_13


  3 / 543 MEDLINE  
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[PMID]:28456984
[Au] Autor:Södergren AL; Ramström S
[Ad] Endereço:Clinical Chemistry, Department of Clinical and Experimental Medicine, Linköping University, SE-58185, Linköping, Sweden. anna.sodergren@liu.se.
[Ti] Título:Detection of Lysosomal Exocytosis in Platelets by Flow Cytometry.
[So] Source:Methods Mol Biol;1594:191-203, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Flow cytometry is a method that allows high throughput analysis of individual cells in suspension. By inclusion of fluorescently labelled antibodies, it is possible to analyze the abundance of one or more surface antigens, such as LAMP-1, without prior lysis of cells. Here we describe the special considerations required for the investigation of lysosomal exocytosis from platelets analyzed with flow cytometry.
[Mh] Termos MeSH primário: Exocitose/fisiologia
Lisossomos/metabolismo
[Mh] Termos MeSH secundário: Plaquetas/metabolismo
Citometria de Fluxo
Seres Humanos
Proteína 1 de Membrana Associada ao Lisossomo/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lysosomal-Associated Membrane Protein 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6934-0_12


  4 / 543 MEDLINE  
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[PMID]:28468680
[Au] Autor:Ferraz R; Cunha CF; Pimentel MIF; Lyra MR; Pereira-Da-Silva T; Schubach AO; Da-Cruz AM; Bertho AL
[Ad] Endereço:Laboratory of Immunoparasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
[Ti] Título:CD3 CD4 CD8 (double negative) T lymphocytes and NKT cells as the main cytotoxic-related-CD107a cells in lesions of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis.
[So] Source:Parasit Vectors;10(1):219, 2017 May 03.
[Is] ISSN:1756-3305
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cutaneous leishmaniasis (CL) is caused by Leishmania (Viannia) braziliensis, which infects dermal macrophages and dendritic cells, causing an intense immune-mediated-tissue inflammation and a skin ulcer with elevated borders that can heal spontaneously or after antimonial therapy. The resolution of lesions depends on an adaptive immune response, and cytotoxic cells seem to have a fundamental role in this process. The aim of this study is to better understand the role of cytotoxicity mediated mechanisms that occur during the immune response in the CL lesion milieu, considering distinct cytotoxic-related CD107a cells, such as CD8 , CD4 , CD4 CD8 (double-negative, DN) and CD4 CD8 (double-positive, DP) T lymphocytes, as well as NK and NKT cells. METHODS: Lesion derived cells were assessed for T cell subpopulations and NK cells, as well as CD107a expression by flow cytometry. In addition, cytometric bead array (CBA) was used to quantify cytokines and granzyme B concentrations in supernatants from macerated lesions. RESULTS: Flow cytometry analyses revealed that NKT cells are the major CD107a-expressing cell population committed to cytotoxicity in CL lesion, although we also observed high frequencies of CD4 and DN T cells expressing CD107a. Analysing the pool of CD107a -cell populations, we found a higher distribution of DN T cells (44%), followed by approximately 25% of NKT cells. Interestingly, NK and CD8 T cells represented only 3 and 4% of the total-CD107a -cell pool, respectively. CONCLUSIONS: The cytotoxicity activity that occurs in the lesion milieu of CL patients seems to be dominated by DN T and NKT cells. These findings suggest the need for a reevaluation of the role of classical-cytotoxic NK and CD8 T cells in the pathogenesis of CL, implicating an important role for other T cell subpopulations.
[Mh] Termos MeSH primário: Citotoxicidade Imunológica
Leishmaniose Cutânea/imunologia
Proteína 1 de Membrana Associada ao Lisossomo/imunologia
Células T Matadoras Naturais/imunologia
Subpopulações de Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Adulto
Antígenos de Protozoários/imunologia
Biópsia
Brasil/epidemiologia
Citocinas/biossíntese
Citocinas/genética
Feminino
Citometria de Fluxo
Granzimas/análise
Seres Humanos
Leishmania braziliensis/imunologia
Leishmaniose Cutânea/epidemiologia
Proteína 1 de Membrana Associada ao Lisossomo/genética
Masculino
Meia-Idade
Pele/imunologia
Pele/parasitologia
Pele/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Cytokines); 0 (Lysosomal-Associated Membrane Protein 1); EC 3.4.21.- (GZMB protein, human); EC 3.4.21.- (Granzymes)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1186/s13071-017-2152-2


  5 / 543 MEDLINE  
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[PMID]:29179214
[Au] Autor:Wang L; Wei Y; Fang W; Lu C; Chen J; Cui G; Diao H
[Ad] Endereço:State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
[Ti] Título:Cetuximab Enhanced the Cytotoxic Activity of Immune Cells during Treatment of Colorectal Cancer.
[So] Source:Cell Physiol Biochem;44(3):1038-1050, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Cetuximab is a chimeric IgG1 monoclonal antibody which targets the extracellular domain of epidermal growth factor receptor. This antibody is widely used for colorectal cancer (CRC) treatment but its influence on the immune system is incompletely understood. METHODS: The immune influence of cetuximab therapy in CRC patients was investigated by analyzing peripheral blood mononuclear cells using flow cytometry. We undertook in vitro cytotoxicity and cytokine-profile assays to ascertain the immunomodulatory effect of cetuximab treatment. RESULTS: The number of CD3+ T, CD8+ T, and natural killer (NK) cells was increased significantly and T-regulatory cells reduced gradually after cetuximab treatment. Percentage of CD4+ T, natural killer T (NKT)-like, invariant NKT, and dendritic cells was similar between baseline patients and cetuximab patients. Expression of CD137 on NK and CD8+ T cells was increased significantly after 4 weeks of cetuximab therapy. In vitro cetuximab treatment markedly increased expression of CD137 and CD107a on NK and CD8+ T cells. Cetuximab treatment promoted the cytotoxic activity of NK and CD8+ T cells against tumor cells. CONCLUSION: Cetuximab treatment promotes activation of the immune response but alleviates immunosuppression: this might be the underlying anti-CRC effect of cetuximab.
[Mh] Termos MeSH primário: Antineoplásicos Imunológicos/uso terapêutico
Cetuximab/uso terapêutico
Neoplasias Colorretais/tratamento farmacológico
Linfócitos/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Antineoplásicos Imunológicos/farmacologia
Linfócitos T CD4-Positivos/citologia
Linfócitos T CD4-Positivos/efeitos dos fármacos
Linfócitos T CD4-Positivos/metabolismo
Linfócitos T CD8-Positivos/citologia
Linfócitos T CD8-Positivos/efeitos dos fármacos
Linfócitos T CD8-Positivos/metabolismo
Células Cultivadas
Cetuximab/farmacologia
Neoplasias Colorretais/patologia
Citocinas/sangue
Feminino
Células HT29
Seres Humanos
Células K562
Células Matadoras Naturais/citologia
Células Matadoras Naturais/efeitos dos fármacos
Células Matadoras Naturais/metabolismo
Leucócitos Mononucleares/citologia
Leucócitos Mononucleares/metabolismo
Linfócitos/citologia
Linfócitos/efeitos dos fármacos
Proteína 1 de Membrana Associada ao Lisossomo/metabolismo
Masculino
Meia-Idade
Linfócitos T Reguladores/citologia
Linfócitos T Reguladores/efeitos dos fármacos
Linfócitos T Reguladores/metabolismo
Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Immunological); 0 (Cytokines); 0 (Lysosomal-Associated Membrane Protein 1); 0 (Tumor Necrosis Factor Receptor Superfamily, Member 9); PQX0D8J21J (Cetuximab)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1159/000485404


  6 / 543 MEDLINE  
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[PMID]:28784930
[Au] Autor:Zwack EE; Feeley EM; Burton AR; Hu B; Yamamoto M; Kanneganti TD; Bliska JB; Coers J; Brodsky IE
[Ad] Endereço:Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
[Ti] Título:Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components.
[So] Source:Infect Immun;85(10), 2017 Oct.
[Is] ISSN:1098-5522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gram-negative bacterial pathogens utilize virulence-associated secretion systems to inject, or translocate, effector proteins into host cells to manipulate cellular processes and promote bacterial replication. However, translocated bacterial products are sensed by ucleotide binding domain and eucine-rich epeat-containing proteins (NLRs), which trigger the formation of a multiprotein complex called the inflammasome, leading to secretion of interleukin-1 (IL-1) family cytokines, pyroptosis, and control of pathogen replication. Pathogenic bacteria inject effector proteins termed Yops, as well as pore-forming proteins that comprise the translocon itself, into target cells. The translocation regulatory protein YopK promotes bacterial virulence by limiting hyperinjection of the translocon proteins YopD and YopB into cells, thereby limiting cellular detection of virulence activity. How hyperinjection of translocon proteins leads to inflammasome activation is currently unknown. We found that translocated YopB and YopD colocalized with the late endosomal/lysosomal protein LAMP1 and that the frequency of YopD and LAMP1 association correlated with the level of caspase-1 activation in individual cells. We also observed colocalization between YopD and Galectin-3, an indicator of endosomal membrane damage. Intriguingly, YopK limited the colocalization of Galectin-3 with YopD, suggesting that YopK limits the induction or sensing of endosomal membrane damage by components of the type III secretion system (T3SS) translocon. Furthermore, guanylate binding proteins (GBPs) encoded on chromosome 3 ( ), which respond to pathogen-induced damage or alteration of host membranes, were necessary for inflammasome activation in response to hyperinjected YopB/-D. Our findings indicate that lysosomal damage by translocon proteins promotes inflammasome activation and implicate GBPs as key regulators of this process.
[Mh] Termos MeSH primário: Proteínas da Membrana Bacteriana Externa/metabolismo
Proteínas de Ligação ao GTP/genética
Inflamassomos/imunologia
Sistemas de Secreção Tipo III/metabolismo
Yersinia pseudotuberculosis/imunologia
[Mh] Termos MeSH secundário: Animais
Proteínas da Membrana Bacteriana Externa/genética
Caspase 1/metabolismo
Linhagem Celular
Citocinas/biossíntese
Citocinas/imunologia
Proteínas de Ligação ao GTP/metabolismo
Galectina 3/metabolismo
Inflamassomos/genética
Inflamassomos/metabolismo
Proteína 1 de Membrana Associada ao Lisossomo/metabolismo
Camundongos
Transporte Proteico
Virulência
Yersinia pseudotuberculosis/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Outer Membrane Proteins); 0 (Cytokines); 0 (Galectin 3); 0 (Inflammasomes); 0 (Lysosomal-Associated Membrane Protein 1); 0 (Type III Secretion Systems); 0 (YopB protein, Yersinia); 0 (YopD protein, Yersinia); EC 3.4.22.36 (Caspase 1); EC 3.6.1.- (GTP-Binding Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE


  7 / 543 MEDLINE  
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[PMID]:28779020
[Au] Autor:Dayam RM; Sun CX; Choy CH; Mancuso G; Glogauer M; Botelho RJ
[Ad] Endereço:Department of Chemistry and Biology, Ryerson University, Toronto, Ontario M5B 2K3, Canada.
[Ti] Título:The Lipid Kinase PIKfyve Coordinates the Neutrophil Immune Response through the Activation of the Rac GTPase.
[So] Source:J Immunol;199(6):2096-2105, 2017 Sep 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neutrophils rapidly arrive at an infection site because of their unparalleled chemotactic ability, after which they unleash numerous attacks on pathogens through degranulation and reactive oxygen species (ROS) production, as well as by phagocytosis, which sequesters pathogens within phagosomes. Phagosomes then fuse with lysosomes and granules to kill the enclosed pathogens. A complex signaling network composed of kinases, GTPases, and lipids, such as phosphoinositides, helps to coordinate all of these processes. There are seven species of phosphoinositides that are interconverted by lipid kinases and phosphatases. PIKfyve is a lipid kinase that generates phosphatidylinositol-3,5-bisphosphate and, directly or indirectly, phosphatidylinositol-5-phosphate [PtdIns(5)P]. PIKfyve inactivation causes massive lysosome swelling, disrupts membrane recycling, and, in macrophages, blocks phagosome maturation. In this study, we explored for the first time, to our knowledge, the role of PIKfyve in human and mouse neutrophils. We show that PIKfyve inhibition in neutrophils does not affect granule morphology or degranulation, but it causes LAMP1 lysosomes to engorge. Additionally, PIKfyve inactivation blocks phagosome-lysosome fusion in a manner that can be rescued, in part, with Ca ionophores or agonists of TRPML1, a lysosomal Ca channel. Strikingly, PIKfyve is necessary for chemotaxis, ROS production, and stimulation of the Rac GTPases, which control chemotaxis and ROS. This is consistent with observations in nonleukocytes that showed that PIKfyve and PtdIns(5)P control Rac and cell migration. Overall, we demonstrate that PIKfyve has a robust role in neutrophils and propose a model in which PIKfyve modulates phagosome maturation through phosphatidylinositol-3,5-bisphosphate-dependent activation of TRPML1, whereas chemotaxis and ROS are regulated by PtdIns(5)P-dependent activation of Rac.
[Mh] Termos MeSH primário: Lisossomos/metabolismo
Neutrófilos/imunologia
Fosfatidilinositol 3-Quinases/metabolismo
[Mh] Termos MeSH secundário: Aminopiridinas/farmacologia
Animais
Degranulação Celular
Células Cultivadas
Quimiotaxia
GTP Fosfo-Hidrolases/metabolismo
Compostos Heterocíclicos com 3 Anéis/farmacologia
Seres Humanos
Proteína 1 de Membrana Associada ao Lisossomo/metabolismo
Fusão de Membrana
Camundongos
Camundongos Endogâmicos
Morfolinas/farmacologia
Fagocitose
Fagossomos/metabolismo
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Fosfatos de Fosfatidilinositol/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Canais de Receptores Transientes de Potencial/metabolismo
Triazinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (6-amino-N-(3-(4-(4-morpholinyl)pyrido(3',2'-4,5)furo(3,2-d)pyrimidin-2-yl)phenyl)-3-pyridinecarboxamide); 0 (Aminopyridines); 0 (Heterocyclic Compounds, 3-Ring); 0 (Lysosomal-Associated Membrane Protein 1); 0 (Mcoln1 protein, mouse); 0 (Morpholines); 0 (Phosphatidylinositol Phosphates); 0 (Reactive Oxygen Species); 0 (Transient Receptor Potential Channels); 0 (Triazines); 0 (phosphatidylinositol 5-phosphate); 5G3P5OK11S (apilimod mesylate); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.137 (Pikfyve protein, mouse); EC 3.6.1.- (GTP Phosphohydrolases)
[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:170806
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601466


  8 / 543 MEDLINE  
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[PMID]:28732201
[Au] Autor:Chen CC; Butz ES; Chao YK; Grishchuk Y; Becker L; Heller S; Slaugenhaupt SA; Biel M; Wahl-Schott C; Grimm C
[Ad] Endereço:Department of Pharmacy, Center for Drug Research and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
[Ti] Título:Small Molecules for Early Endosome-Specific Patch Clamping.
[So] Source:Cell Chem Biol;24(7):907-916.e4, 2017 Jul 20.
[Is] ISSN:2451-9456
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To resolve the subcellular distribution of endolysosomal ion channels, we have established a novel experimental approach to selectively patch clamp Rab5 positive early endosomes (EE) versus Rab7/LAMP1-positive late endosomes/lysosomes (LE/LY). To functionally characterize ion channels in endolysosomal membranes with the patch-clamp technique, it is important to develop techniques to selectively enlarge the respective organelles. We found here that two small molecules, wortmannin and latrunculin B, enlarge Rab5-positive EE when combined but not Rab7-, LAMP1-, or Rab11 (RE)-positive vesicles. The two compounds act rapidly, specifically, and are readily applicable in contrast to genetic approaches or previously used compounds such as vacuolin, which enlarges EE, RE, and LE/LY. We apply this approach here to measure currents mediated by TRPML channels, in particular TRPML3, which we found to be functionally active in both EE and LE/LY in overexpressing cells as well as in endogenously expressing CD11b+ lung-tissue macrophages.
[Mh] Termos MeSH primário: Potenciais de Ação/efeitos dos fármacos
Androstadienos/farmacologia
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia
Endossomos/metabolismo
Tiazolidinas/farmacologia
[Mh] Termos MeSH secundário: Aminopiridinas/farmacologia
Antígeno CD11b/metabolismo
Endossomos/efeitos dos fármacos
Células HEK293
Compostos Heterocíclicos com 3 Anéis/farmacologia
Seres Humanos
Pulmão/citologia
Pulmão/metabolismo
Proteína 1 de Membrana Associada ao Lisossomo/metabolismo
Lisossomos/efeitos dos fármacos
Lisossomos/metabolismo
Macrófagos/citologia
Macrófagos/efeitos dos fármacos
Macrófagos/metabolismo
Macrófagos Peritoneais/citologia
Macrófagos Peritoneais/efeitos dos fármacos
Macrófagos Peritoneais/metabolismo
Técnicas de Patch-Clamp
Canais de Receptores Transientes de Potencial/genética
Canais de Receptores Transientes de Potencial/metabolismo
Proteínas rab de Ligação ao GTP/metabolismo
Proteínas rab5 de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (6-amino-N-(3-(4-(4-morpholinyl)pyrido(3',2'-4,5)furo(3,2-d)pyrimidin-2-yl)phenyl)-3-pyridinecarboxamide); 0 (Aminopyridines); 0 (Androstadienes); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (CD11b Antigen); 0 (Heterocyclic Compounds, 3-Ring); 0 (Lysosomal-Associated Membrane Protein 1); 0 (MCOLN1 protein, human); 0 (MCOLN3 protein, human); 0 (Thiazolidines); 0 (Transient Receptor Potential Channels); 152989-05-4 (rab7 protein); EC 3.6.1.- (rab11 protein); EC 3.6.5.2 (rab GTP-Binding Proteins); EC 3.6.5.2 (rab5 GTP-Binding Proteins); LW7U308U7U (latrunculin B); XVA4O219QW (wortmannin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE


  9 / 543 MEDLINE  
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[PMID]:28669030
[Au] Autor:Moulin M; Alguacil J; Gu S; Mehtougui A; Adams EJ; Peyrottes S; Champagne E
[Ad] Endereço:Centre de Physiopathologie de Toulouse Purpan, CPTP, INSERM U1043/CNRS UMR5282, 31024, Toulouse, France.
[Ti] Título:Vγ9Vδ2 T cell activation by strongly agonistic nucleotidic phosphoantigens.
[So] Source:Cell Mol Life Sci;74(23):4353-4367, 2017 Dec.
[Is] ISSN:1420-9071
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Human Vγ9Vδ2 T cells can sense through their TCR tumor cells producing the weak endogenous phosphorylated antigen isopentenyl pyrophosphate (IPP), or bacterially infected cells producing the strong agonist hydroxyl dimethylallyl pyrophosphate (HDMAPP). The recognition of the phosphoantigen is dependent on its binding to the intracellular B30.2 domain of butyrophilin BTN3A1. Most studies have focused on pyrophosphate phosphoantigens. As triphosphate nucleotide derivatives are naturally co-produced with IPP and HDMAPP, we analyzed their specific properties using synthetic nucleotides derived from HDMAPP. The adenylated, thymidylated and uridylated triphosphate derivatives were found to activate directly Vγ9Vδ2 cell lines as efficiently as HDMAPP in the absence of accessory cells. These antigens were inherently resistant to terminal phosphatases, but apyrase, when added during a direct stimulation of Vγ9Vδ2 cells, abrogated their stimulating activity, indicating that their activity required transformation into strong pyrophosphate agonists by a nucleotide pyrophosphatase activity which is present in serum. Tumor cells can be sensitized with nucleotide phosphoantigens in the presence of apyrase to become stimulatory, showing that this can occur before their hydrolysis into pyrophosphates. Whereas tumors sensitized with HDMAPP rapidly lost their stimulatory activity, sensitization with nucleotide derivatives, in particular with the thymidine derivative, induced long-lasting stimulating ability. Using isothermal titration calorimetry, binding of some nucleotide derivatives to BTN3A1 intracellular domain was found to occur with an affinity similar to that of IPP, but much lower than that of HDMAPP. Thus, nucleotide phosphoantigens are precursors of pyrophosphate antigens which can deliver strong agonists intracellularly resulting in prolonged and strengthened activity.
[Mh] Termos MeSH primário: Antígenos CD/genética
Butirofilinas/genética
Hemiterpenos/farmacologia
Ativação Linfocitária/efeitos dos fármacos
Organofosfatos/farmacologia
Compostos Organofosforados/farmacologia
Receptores de Antígenos de Linfócitos T gama-delta/genética
Linfócitos T/efeitos dos fármacos
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/análogos & derivados
Trifosfato de Adenosina/farmacologia
Antígenos/farmacologia
Antígenos CD/imunologia
Butirofilinas/imunologia
Relação Dose-Resposta Imunológica
Células HeLa
Seres Humanos
Interferon gama/biossíntese
Interferon gama/imunologia
Células K562
Proteína 1 de Membrana Associada ao Lisossomo/biossíntese
Proteína 1 de Membrana Associada ao Lisossomo/imunologia
Cultura Primária de Células
Receptores de Antígenos de Linfócitos T gama-delta/classificação
Receptores de Antígenos de Linfócitos T gama-delta/imunologia
Linfócitos T/citologia
Linfócitos T/imunologia
Fator de Necrose Tumoral alfa/biossíntese
Fator de Necrose Tumoral alfa/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-hydroxy-3-methyl-2-butenyl diphosphate); 0 (Antigens); 0 (Antigens, CD); 0 (BTN3A1 protein, human); 0 (Butyrophilins); 0 (Hemiterpenes); 0 (Lysosomal-Associated Membrane Protein 1); 0 (Organophosphates); 0 (Organophosphorus Compounds); 0 (Receptors, Antigen, T-Cell, gamma-delta); 0 (Tumor Necrosis Factor-alpha); 0 (triphosphoric acid 1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) ester); 358-71-4 (isopentenyl pyrophosphate); 82115-62-6 (Interferon-gamma); 8L70Q75FXE (Adenosine Triphosphate)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170703
[St] Status:MEDLINE
[do] DOI:10.1007/s00018-017-2583-0


  10 / 543 MEDLINE  
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[PMID]:28607115
[Au] Autor:Leone DA; Peschel A; Brown M; Schachner H; Ball MJ; Gyuraszova M; Salzer-Muhar U; Fukuda M; Vizzardelli C; Bohle B; Rees AJ; Kain R
[Ad] Endereço:Clinical Institute of Pathology, Medical University of Vienna, Vienna 1090, Austria; renate.kain@meduniwien.ac.at dario.leone@meduniwien.ac.at.
[Ti] Título:Surface LAMP-2 Is an Endocytic Receptor That Diverts Antigen Internalized by Human Dendritic Cells into Highly Immunogenic Exosomes.
[So] Source:J Immunol;199(2):531-546, 2017 Jul 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The lysosome-associated membrane protein (LAMP) family includes the dendritic cell endocytic receptors DC-LAMP and CD68, as well as LAMP-1 and LAMP-2. In this study we identify LAMP-1 (CD107a) and LAMP-2 (CD107b) on the surface of human monocyte-derived dendritic cells (MoDC) and show only LAMP-2 is internalized after ligation by specific Abs, including H4B4, and traffics rapidly but transiently to the MHC class II loading compartment, as does Ag conjugated to H4B4. However, pulsing MoDC with conjugates of primary (keyhole limpet hemocyanin; KLH) and recall (Bet v 1) Ags (H4B4*KLH and H4B4*Bet v 1) induced significantly less CD4 cell proliferation than pulsing with native Ag or Ag conjugated to control mAb (ISO*KLH and ISO*Bet v 1). In H4B4*KLH-pulsed MoDC, the duration of KLH residence in MHC class II loading compartments was significantly reduced, as were surface HLA-DR and DR-bound KLH-derived peptides. Paradoxically, MoDC pulsed with H4B4*KLH, but not the other KLH preparations, induced robust proliferation of CD4 cells separated from them by a transwell membrane, indicating factors in the supernatant were responsible. Furthermore, extracellular vesicles from supernatants of H4B4*KLH-pulsed MoDC contained significantly more HLA-DR and KLH than those purified from control MoDC, and KLH was concentrated specifically in exosomes that were a uniquely effective source of Ag in standard T cell proliferation assays. In summary, we identify LAMP-2 as an endocytic receptor on human MoDC that routes cargo into unusual Ag processing pathways, which reduces surface expression of Ag-derived peptides while selectively enriching Ag within immunogenic exosomes. This novel pathway has implications for the initiation of immune responses both locally and at distant sites.
[Mh] Termos MeSH primário: Apresentação do Antígeno
Células Dendríticas/imunologia
Exossomos/imunologia
Proteína 2 de Membrana Associada ao Lisossomo/metabolismo
[Mh] Termos MeSH secundário: Animais
Formação de Anticorpos
Linfócitos T CD4-Positivos/imunologia
Antígenos HLA/imunologia
Hemocianinas/imunologia
Seres Humanos
Ativação Linfocitária
Proteína 1 de Membrana Associada ao Lisossomo/genética
Proteína 1 de Membrana Associada ao Lisossomo/imunologia
Proteína 2 de Membrana Associada ao Lisossomo/genética
Proteína 2 de Membrana Associada ao Lisossomo/imunologia
Camundongos
Monócitos/imunologia
Peptídeos/imunologia
Receptores de Superfície Celular/imunologia
Receptores de Superfície Celular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HLA Antigens); 0 (LAMP2 protein, human); 0 (Lysosomal-Associated Membrane Protein 1); 0 (Lysosomal-Associated Membrane Protein 2); 0 (Peptides); 0 (Receptors, Cell Surface); 9013-72-3 (Hemocyanins); FV4Y0JO2CX (keyhole-limpet hemocyanin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601263



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