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dc.contributor.author
Carestia, Agostina
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dc.contributor.author
Rivadeneyra, Leonardo
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dc.contributor.author
Romaniuk, María Albertina
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dc.contributor.author
Fondevila, Carlos
dc.contributor.author
Negrotto, Soledad
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dc.contributor.author
Schattner, Mirta Ana
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dc.date.available
2017-07-21T15:25:20Z
dc.date.issued
2013-11
dc.identifier.citation
Carestia, Agostina; Rivadeneyra, Leonardo; Romaniuk, María Albertina; Fondevila, Carlos; Negrotto, Soledad; et al.; Functional responses and molecular mechanisms involved in histone-mediated platelet activation; Schattauer Gmbh-Verlag Medizin Naturwissenschaften; Thrombosis and Haemostasis; 110; 5; 11-2013; 1335-1345
dc.identifier.issn
0340-6245
dc.identifier.uri
http://hdl.handle.net/11336/21061
dc.description.abstract
Histones are highly alkaline proteins found in cell nuclei and they can be released by either dying or inflammatory cells. The recent observations that histones are major components of neutrophil extracellular traps and promote platelet aggregation and platelet-dependent thrombin generation have shown that these proteins are potent prothrombotic molecules. Because the mechanism(s) of platelet activation by histones are not completely understood, we explored the ability of individual recombinant human histones H1, H2A, H2B, H3 and H4 to induce platelet activation as well as the possible molecular mechanisms involved. All histones were substrates for platelet adhesion and spreading and triggered fibrinogen binding, aggregation, von Willebrand factor release, P-selectin and phosphatidylserine (PS) exposure and the formation of platelet-leukocyte aggregates; however, H4 was the most potent. Histone-mediated fibrinogen binding, P-selectin and PS exposure and the formation of mixed aggregates were potentiated by thrombin. Histones induced the activation of ERK, Akt, p38 and NFκB. Accordingly, histone-induced platelet activation was significantly impaired by pretreatment of platelets with inhibitors of ERK (U 0126), PI3K/Akt (Ly 294002), p38 (SB 203580) and NFκB (BAY 11-7082 and Ro 106-9920). Preincubation of platelets with either aspirin or dexamethasone markedly decreased fibrinogen binding and the adhesion mediated by histones without affecting P-selectin exposure. Functional platelet responses induced by H3 and H4, but not H1, H2A and H2B, were partially mediated through interaction with Toll-like receptors -2 and -4. Our data identify histones as important triggers of haemostatic and proinflammatory platelet responses, and only haemostatic responses are partially inhibited by anti-inflammatory drugs.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Schattauer Gmbh-Verlag Medizin Naturwissenschaften
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Histones
dc.subject
Platelets
dc.subject
Nets
dc.subject
Inflammation
dc.subject
Neutrophil Extracellular Traps
dc.subject.classification
Otras Medicina Básica
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Functional responses and molecular mechanisms involved in histone-mediated platelet activation
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-07-17T21:14:28Z
dc.journal.volume
110
dc.journal.number
5
dc.journal.pagination
1335-1345
dc.journal.pais
Alemania
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dc.journal.ciudad
Stuttgart
dc.description.fil
Fil: Carestia, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Rivadeneyra, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Fondevila, Carlos. Clínica Bazterrica;
dc.description.fil
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.journal.title
Thrombosis and Haemostasis
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://th.schattauer.de/en/contents/archive/issue/1803/manuscript/20167.html
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1160/TH13-02-0174
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