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AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study

BACKGROUND: The C-allele of the aquaporin (AQP5) -1364A/C polymorphism is associated with decreased AQP5 expression but increased 30-day survival in patients with severe sepsis. AQP5 expression might affect survival via an impact on cell migration. Consequently, we tested the hypothesis that (1) Aqp...

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Autores principales: Rump, Katharina, Unterberg, Matthias, Bergmann, Lars, Bankfalvi, Agnes, Menon, Anil, Schäfer, Simon, Scherag, André, Bazzi, Zainab, Siffert, Winfried, Peters, Jürgen, Adamzik, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117689/
https://www.ncbi.nlm.nih.gov/pubmed/27871297
http://dx.doi.org/10.1186/s12967-016-1079-2
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author Rump, Katharina
Unterberg, Matthias
Bergmann, Lars
Bankfalvi, Agnes
Menon, Anil
Schäfer, Simon
Scherag, André
Bazzi, Zainab
Siffert, Winfried
Peters, Jürgen
Adamzik, Michael
author_facet Rump, Katharina
Unterberg, Matthias
Bergmann, Lars
Bankfalvi, Agnes
Menon, Anil
Schäfer, Simon
Scherag, André
Bazzi, Zainab
Siffert, Winfried
Peters, Jürgen
Adamzik, Michael
author_sort Rump, Katharina
collection PubMed
description BACKGROUND: The C-allele of the aquaporin (AQP5) -1364A/C polymorphism is associated with decreased AQP5 expression but increased 30-day survival in patients with severe sepsis. AQP5 expression might affect survival via an impact on cell migration. Consequently, we tested the hypothesis that (1) Aqp5 knockout (KO) compared to wild type (WT) mice show an increased survival following lipopolysaccharide (LPS) administration, and that (2) AQP5 expression and the AQP5 -1364A/C polymorphism alters immune cell migration. METHODS: We investigated Aqp5-KO and wild type mice after intraperitoneal injection of either E.coli lipopolysaccharide (LPS, serotype O127:B8, 20 mg/kg) or saline. Furthermore, neutrophils of volunteers with the AA-AQP5 or AC/CC-AQP5- genotype were incubated with 10(−8) M Chemotactic peptide (fMLP) and their migration was assessed by a filter migration assay. Additionally, AQP5 expression after fMLP incubation was analyzed by RT-PCR and Western blot. Moreover, migration of AQP5 overexpressing Jurkat cells was studied after SDF-1α-stimulation. We used exact Wilcoxon–Mann–Whitney tests; exact Wilcoxon signed-rank tests and the Kaplan–Meier estimator for statistical analysis. RESULTS: Fifty-six percent of Aqp5-KO but only 22% of WT mice survived following LPS-injection. WT mice showed increased neutrophil migration into peritoneum and lung compared to Aqp5-KO mice. Target-oriented migration of neutrophils was seen after 0.5 h in AA-genotype cells but only after 1.5 h in AC/CC-genotype cells, with a threefold lower migrating cell count. AQP5 overexpressing Jurkat cells showed a 2.4 times stronger migration compared to native Jurkat cells. CONCLUSION: The AQP5 genotype may influence survival following LPS by altering neutrophil cell migration. Trial registration DRKS00010437. Retrospectively registered 26 April 2016 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-1079-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-51176892016-11-28 AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study Rump, Katharina Unterberg, Matthias Bergmann, Lars Bankfalvi, Agnes Menon, Anil Schäfer, Simon Scherag, André Bazzi, Zainab Siffert, Winfried Peters, Jürgen Adamzik, Michael J Transl Med Research BACKGROUND: The C-allele of the aquaporin (AQP5) -1364A/C polymorphism is associated with decreased AQP5 expression but increased 30-day survival in patients with severe sepsis. AQP5 expression might affect survival via an impact on cell migration. Consequently, we tested the hypothesis that (1) Aqp5 knockout (KO) compared to wild type (WT) mice show an increased survival following lipopolysaccharide (LPS) administration, and that (2) AQP5 expression and the AQP5 -1364A/C polymorphism alters immune cell migration. METHODS: We investigated Aqp5-KO and wild type mice after intraperitoneal injection of either E.coli lipopolysaccharide (LPS, serotype O127:B8, 20 mg/kg) or saline. Furthermore, neutrophils of volunteers with the AA-AQP5 or AC/CC-AQP5- genotype were incubated with 10(−8) M Chemotactic peptide (fMLP) and their migration was assessed by a filter migration assay. Additionally, AQP5 expression after fMLP incubation was analyzed by RT-PCR and Western blot. Moreover, migration of AQP5 overexpressing Jurkat cells was studied after SDF-1α-stimulation. We used exact Wilcoxon–Mann–Whitney tests; exact Wilcoxon signed-rank tests and the Kaplan–Meier estimator for statistical analysis. RESULTS: Fifty-six percent of Aqp5-KO but only 22% of WT mice survived following LPS-injection. WT mice showed increased neutrophil migration into peritoneum and lung compared to Aqp5-KO mice. Target-oriented migration of neutrophils was seen after 0.5 h in AA-genotype cells but only after 1.5 h in AC/CC-genotype cells, with a threefold lower migrating cell count. AQP5 overexpressing Jurkat cells showed a 2.4 times stronger migration compared to native Jurkat cells. CONCLUSION: The AQP5 genotype may influence survival following LPS by altering neutrophil cell migration. Trial registration DRKS00010437. Retrospectively registered 26 April 2016 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-1079-2) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-21 /pmc/articles/PMC5117689/ /pubmed/27871297 http://dx.doi.org/10.1186/s12967-016-1079-2 Text en © The Author(s) 2016 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
Rump, Katharina
Unterberg, Matthias
Bergmann, Lars
Bankfalvi, Agnes
Menon, Anil
Schäfer, Simon
Scherag, André
Bazzi, Zainab
Siffert, Winfried
Peters, Jürgen
Adamzik, Michael
AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study
title AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study
title_full AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study
title_fullStr AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study
title_full_unstemmed AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study
title_short AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study
title_sort aqp5-1364a/c polymorphism and the aqp5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117689/
https://www.ncbi.nlm.nih.gov/pubmed/27871297
http://dx.doi.org/10.1186/s12967-016-1079-2
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