AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration

  • \(\textbf {Background:}\) 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) \(\it Aqp5\) 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. \(\textbf {Methods:}\) We investigated \(\it Aqp5\)-KO and wild type mice after intraperitoneal injection of either \(\textit {E.coli}\) lipopolysaccharide (LPS, serotype O127:B8, 20 mg/kg) or saline. Furthermore, neutrophils of volunteers with the \(\textit {AA-AQP5}\) or AC/CC-\(\it AQP5\)- 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. \(\textbf {Results:}\) Fifty-six percent of \(\it Aqp5\)-KO but only 22% of WT mice survived following LPS-injection. WT mice showed increased neutrophil migration into peritoneum and lung compared to \(\it Aqp5\)-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. \(\textbf {Conclusion:}\) The \(\it AQP5\) genotype may influence survival following LPS by altering neutrophil cell migration.

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Metadaten
Author:Katharina RumpORCiDGND, Matthias UnterbergORCiDGND, Lars BergmannORCiDGND, Ágnes BánkfalviGND, Anil MenonGND, Simon SchäferORCiDGND, André ScheragGND, Zainab BazziGND, Winfried SiffertGND, Jürgen PetersGND, Michael AdamzikORCiDGND
URN:urn:nbn:de:hbz:294-58486
DOI:https://doi.org/10.1186/s12967-016-1079-2
Parent Title (English):Journal of translational medicine
Subtitle (English):a prospective laboratory and patient study
Document Type:Article
Language:English
Date of Publication (online):2018/07/05
Date of first Publication:2016/11/21
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
Volume:14
Issue:1
First Page:321-1
Last Page:321-11
Note:
Article Processing Charge funded by the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Knappschaftskrankenhaus Bochum, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie
Dewey Decimal Classification:Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit
open_access (DINI-Set):open_access
faculties:Medizinische Fakultät
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International