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Título: | A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection |
Fecha de publicación: | 2019 |
Editorial: | Nature Research |
Cita bibliográfica: | Nature Microbiology, vol. 4 (2019), 2442–2455 |
ISSN: | Electronic: 2058-5276 |
Palabras clave: | Antithrombin Inflammation Bacterial infection |
Resumen: | Severe infectious diseases are often characterized by an overwhelming and unbalanced systemic immune response to microbial infections. Human antithrombin (hAT) is a crucial coagulation inhibitor with anti-inflammatory activities. Here we identify three hAT-binding proteins (CD13, CD300f and LRP-1) on human monocytes that are involved in blocking the activity of nuclear factor-κB. We found that the modulating effect is primarily restricted to the less abundant β-isoform (hβAT) of hAT that lacks N-glycosylation at position 135. Individuals with a mutation at this position have increased production of hβAT and analysis of their blood, which was stimulated ex vivo with lipopolysaccharide, showed a decreased inflammatory response. Similar findings were recorded when heterozygotic mice expressing hAT or hβAT were challenged with lipopolysaccharide or infected with Escherichia coli bacteria. Our results finally demonstrate that in a lethal E. coli infection model, survival rates increased when mice were treated with hβAT one hour and five hours after infection. The treatment also resulted in a reduction of the inflammatory response and less severe organ damage. |
Autor/es principal/es: | Papareddy, Praveen Rossnagel, Madlen Hollwedel, Femke Kilic, Gülcan Veerla, Srinivas Naudin, Clément Smeds, Emanuel Westman, Johannes Martínez-Martínez, Irene Egesten, Arne Morena-Barrio, María Eugenia de la Corral, Javier Linder, Adam Artoni, Andrea Abbattista, Maria Novembrino, Cristina Brakebusch, Cord Hebert Martinelli, Ida Kasetty, Gopinath Herwarld, Heiko |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Medicina |
URI: | http://hdl.handle.net/10201/139224 |
DOI: | https://doi.org/10.1038/s41564-019-0559-6 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 18 |
Derechos: | info:eu-repo/semantics/embargoedAccess |
Descripción: | ©The Author(s), under exclusive licence to Springer Nature Limited 2019. This document is the Published version of a Published Work that appeared in final form in Nature Microbiology. To access the final edited and published work see https://doi.org/10.1038/s41564-019-0559-6 |
Aparece en las colecciones: | Artículos: Medicina |
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