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