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Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response
Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditar...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806930/ https://www.ncbi.nlm.nih.gov/pubmed/27010826 http://dx.doi.org/10.1371/journal.pgen.1005935 |
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author | Ojeda-Fernández, Luisa Recio-Poveda, Lucía Aristorena, Mikel Lastres, Pedro Blanco, Francisco J. Sanz-Rodríguez, Francisco Gallardo-Vara, Eunate de las Casas-Engel, Mateo Corbí, Ángel Arthur, Helen M. Bernabeu, Carmelo Botella, Luisa M. |
author_facet | Ojeda-Fernández, Luisa Recio-Poveda, Lucía Aristorena, Mikel Lastres, Pedro Blanco, Francisco J. Sanz-Rodríguez, Francisco Gallardo-Vara, Eunate de las Casas-Engel, Mateo Corbí, Ángel Arthur, Helen M. Bernabeu, Carmelo Botella, Luisa M. |
author_sort | Ojeda-Fernández, Luisa |
collection | PubMed |
description | Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-Osler-Weber syndrome. Endoglin is also expressed in human macrophages, but its role in macrophage function remains unknown. In this work, we show that endoglin expression is triggered during the monocyte-macrophage differentiation process, both in vitro and during the in vivo differentiation of blood monocytes recruited to foci of inflammation in wild-type C57BL/6 mice. To analyze the role of endoglin in macrophages in vivo, an endoglin myeloid lineage specific knock-out mouse line (Eng(fl/fl)LysMCre) was generated. These mice show a predisposition to develop spontaneous infections by opportunistic bacteria. Eng(fl/fl)LysMCre mice also display increased survival following LPS-induced peritonitis, suggesting a delayed immune response. Phagocytic activity is impaired in peritoneal macrophages, altering one of the main functions of macrophages which contributes to the initiation of the immune response. We also observed altered expression of TGF-β1 target genes in endoglin deficient peritoneal macrophages. Overall, the altered immune activity of endoglin deficient macrophages could help to explain the higher rate of infectious diseases seen in HHT1 patients. |
format | Online Article Text |
id | pubmed-4806930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48069302016-03-25 Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response Ojeda-Fernández, Luisa Recio-Poveda, Lucía Aristorena, Mikel Lastres, Pedro Blanco, Francisco J. Sanz-Rodríguez, Francisco Gallardo-Vara, Eunate de las Casas-Engel, Mateo Corbí, Ángel Arthur, Helen M. Bernabeu, Carmelo Botella, Luisa M. PLoS Genet Research Article Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-Osler-Weber syndrome. Endoglin is also expressed in human macrophages, but its role in macrophage function remains unknown. In this work, we show that endoglin expression is triggered during the monocyte-macrophage differentiation process, both in vitro and during the in vivo differentiation of blood monocytes recruited to foci of inflammation in wild-type C57BL/6 mice. To analyze the role of endoglin in macrophages in vivo, an endoglin myeloid lineage specific knock-out mouse line (Eng(fl/fl)LysMCre) was generated. These mice show a predisposition to develop spontaneous infections by opportunistic bacteria. Eng(fl/fl)LysMCre mice also display increased survival following LPS-induced peritonitis, suggesting a delayed immune response. Phagocytic activity is impaired in peritoneal macrophages, altering one of the main functions of macrophages which contributes to the initiation of the immune response. We also observed altered expression of TGF-β1 target genes in endoglin deficient peritoneal macrophages. Overall, the altered immune activity of endoglin deficient macrophages could help to explain the higher rate of infectious diseases seen in HHT1 patients. Public Library of Science 2016-03-24 /pmc/articles/PMC4806930/ /pubmed/27010826 http://dx.doi.org/10.1371/journal.pgen.1005935 Text en © 2016 Ojeda-Fernández et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ojeda-Fernández, Luisa Recio-Poveda, Lucía Aristorena, Mikel Lastres, Pedro Blanco, Francisco J. Sanz-Rodríguez, Francisco Gallardo-Vara, Eunate de las Casas-Engel, Mateo Corbí, Ángel Arthur, Helen M. Bernabeu, Carmelo Botella, Luisa M. Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response |
title | Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response |
title_full | Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response |
title_fullStr | Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response |
title_full_unstemmed | Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response |
title_short | Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response |
title_sort | mice lacking endoglin in macrophages show an impaired immune response |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806930/ https://www.ncbi.nlm.nih.gov/pubmed/27010826 http://dx.doi.org/10.1371/journal.pgen.1005935 |
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