title: AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study.
abstract: 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.
  
  
  
  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 10-8M 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.
  
  
  
  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.
  
  
  
  The AQP5 genotype may influence survival following LPS by altering neutrophil cell migration. Trial registration DRKS00010437. Retrospectively registered 26 April 2016.
authors.affiliation: Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum-Langendreer, In der Schornau 55, 45882, Bochum, Germany. katharina.k.rump@rub.de.|Institut für Pharmakogenetik, Universität Duisburg-Essen, Duisburg, Germany. katharina.k.rump@rub.de.|Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum and Universität Duisburg-Essen, Essen, Germany. katharina.k.rump@rub.de.
authors.forename: Katharina
authors.identifier: 0000-0003-2220-519X
authors.initials: K
authors.lastname: Rump
authors.affiliation: Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum-Langendreer, In der Schornau 55, 45882, Bochum, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Unterberg
authors.affiliation: Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum-Langendreer, In der Schornau 55, 45882, Bochum, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Bergmann
authors.affiliation: Institut für Pathologie, Universitätsklinikum and Universität Duisburg-Essen, Essen, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Bankfalvi
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Menon
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum and Universität Duisburg-Essen, Essen, Germany.|Klinik für Anästhesiologie, LMU, Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schäfer
authors.affiliation: Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.affiliation: Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum-Langendreer, In der Schornau 55, 45882, Bochum, Germany.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Bazzi
authors.affiliation: Institut für Pharmakogenetik, Universität Duisburg-Essen, Duisburg, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Siffert
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum and Universität Duisburg-Essen, Essen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
authors.affiliation: Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum-Langendreer, In der Schornau 55, 45882, Bochum, Germany.|Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum and Universität Duisburg-Essen, Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Adamzik
mesh_terms: D000818:Animals; D051402:Aquaporin 5 / Q000235:genetics*; D015153:Blotting, Western; D002465:Cell Movement; D016207:Cytokines / Q000097:blood; D005786:Gene Expression Regulation; D005838:Genotype; D018922:HL-60 Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D019169:Jurkat Cells; D008070:Lipopolysaccharides; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D016019:Survival Analysis
chemical_list: C496036:AQP5 protein, human; C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D016207:Cytokines; D008070:Lipopolysaccharides