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Experimental murine acute lung injury induces increase of pulmonary TIE2-expressing macrophages

BACKGROUND: Breakdown of the alveolo-capillary wall is pathognomonic for Acute Lung Injury (ALI). Angiopoietins, vascular-specific growth factors, are linked to endothelial barrier dysfunction, and elevated Angiopoietin-2 (ANG2) levels are associated with poor outcome of ALI patients. Specialized im...

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Autores principales: Ehrentraut, Heidi, Weisheit, Christina, Scheck, Marcel, Frede, Stilla, Hilbert, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001122/
https://www.ncbi.nlm.nih.gov/pubmed/29946226
http://dx.doi.org/10.1186/s12950-018-0188-5
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author Ehrentraut, Heidi
Weisheit, Christina
Scheck, Marcel
Frede, Stilla
Hilbert, Tobias
author_facet Ehrentraut, Heidi
Weisheit, Christina
Scheck, Marcel
Frede, Stilla
Hilbert, Tobias
author_sort Ehrentraut, Heidi
collection PubMed
description BACKGROUND: Breakdown of the alveolo-capillary wall is pathognomonic for Acute Lung Injury (ALI). Angiopoietins, vascular-specific growth factors, are linked to endothelial barrier dysfunction, and elevated Angiopoietin-2 (ANG2) levels are associated with poor outcome of ALI patients. Specialized immune cells, referred to as ‘TIE2-expressing monocytes and macrophages’ (TEM), were shown to specifically respond to ANG2 binding. However, their involvement in acute inflammatory processes is so far completely undescribed. Thus, our aim was to assess the dynamics of TEMs in a murine model of ALI. RESULTS: Intratracheal instillation of LPS induced a robust pulmonary pro-inflammatory response with endothelial barrier dysfunction and significantly enhanced ANG2 expression. The percentage number of TEMs, assessed by FACS analysis, was more than trebled compared to controls, with TEM count in lungs reaching more than 40% of all macrophages. Such distinct dynamic was absent in all other analyzed compartments (alveolar space, spleen, blood). Incubation of the monocytic cell line THP-1 with LPS or TNF-α resulted in a dose-dependent, significant upregulation of TIE2, suggesting that not recruitment from extra-pulmonary compartments but TIE2 upregulation in resident macrophages accounts for increased lung TEM frequencies. CONCLUSIONS: For the first time, our data provide evidence that the activity of TEMs changes at sites of acute inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12950-018-0188-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-60011222018-06-26 Experimental murine acute lung injury induces increase of pulmonary TIE2-expressing macrophages Ehrentraut, Heidi Weisheit, Christina Scheck, Marcel Frede, Stilla Hilbert, Tobias J Inflamm (Lond) Research BACKGROUND: Breakdown of the alveolo-capillary wall is pathognomonic for Acute Lung Injury (ALI). Angiopoietins, vascular-specific growth factors, are linked to endothelial barrier dysfunction, and elevated Angiopoietin-2 (ANG2) levels are associated with poor outcome of ALI patients. Specialized immune cells, referred to as ‘TIE2-expressing monocytes and macrophages’ (TEM), were shown to specifically respond to ANG2 binding. However, their involvement in acute inflammatory processes is so far completely undescribed. Thus, our aim was to assess the dynamics of TEMs in a murine model of ALI. RESULTS: Intratracheal instillation of LPS induced a robust pulmonary pro-inflammatory response with endothelial barrier dysfunction and significantly enhanced ANG2 expression. The percentage number of TEMs, assessed by FACS analysis, was more than trebled compared to controls, with TEM count in lungs reaching more than 40% of all macrophages. Such distinct dynamic was absent in all other analyzed compartments (alveolar space, spleen, blood). Incubation of the monocytic cell line THP-1 with LPS or TNF-α resulted in a dose-dependent, significant upregulation of TIE2, suggesting that not recruitment from extra-pulmonary compartments but TIE2 upregulation in resident macrophages accounts for increased lung TEM frequencies. CONCLUSIONS: For the first time, our data provide evidence that the activity of TEMs changes at sites of acute inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12950-018-0188-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-14 /pmc/articles/PMC6001122/ /pubmed/29946226 http://dx.doi.org/10.1186/s12950-018-0188-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ehrentraut, Heidi
Weisheit, Christina
Scheck, Marcel
Frede, Stilla
Hilbert, Tobias
Experimental murine acute lung injury induces increase of pulmonary TIE2-expressing macrophages
title Experimental murine acute lung injury induces increase of pulmonary TIE2-expressing macrophages
title_full Experimental murine acute lung injury induces increase of pulmonary TIE2-expressing macrophages
title_fullStr Experimental murine acute lung injury induces increase of pulmonary TIE2-expressing macrophages
title_full_unstemmed Experimental murine acute lung injury induces increase of pulmonary TIE2-expressing macrophages
title_short Experimental murine acute lung injury induces increase of pulmonary TIE2-expressing macrophages
title_sort experimental murine acute lung injury induces increase of pulmonary tie2-expressing macrophages
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001122/
https://www.ncbi.nlm.nih.gov/pubmed/29946226
http://dx.doi.org/10.1186/s12950-018-0188-5
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