title: Induced expression and functional effects of aquaporin-1 in human leukocytes in sepsis.
abstract: BACKGROUND
  Gene expression profiling was performed via DNA microarrays in leukocytes from critically ill trauma patients nonseptic upon admission to the ICU, who subsequently developed either sepsis (n = 2) or severe sepsis and acute respiratory distress syndrome (n = 3). By comparing our results with published expression profiling studies in animal models of sepsis and lung injury, we found aquaporin-1 to be differentially expressed across all studies. Our aim was to determine how the water channel aquaporin-1 is involved in regulating the immune response in critically ill patients during infection acquired in the ICU.
  
  
  METHODS
  Following the results of the initial genetic screening study, we prospectively followed aquaporin-1 leukocyte expression patterns in patients with ICU-acquired sepsis who subsequently developed septic shock (n = 16) versus critically ill patients who were discharged without developing sepsis (n = 13). We additionally determined aquaporin-1 expression upon lipopolysaccharide (LPS) exposure and explored functional effects of aquaporin-1 induction in polymorphonuclear granulocytes (PMNs).
  
  
  RESULTS
  Leukocyte aquaporin-1 expression was induced at the onset of sepsis (median 1.71-fold increase; interquartile range: 0.99 to 2.42, P = 0.012 from baseline) and was further increased upon septic shock (median 3.00-fold increase; interquartile range: 1.20 to 5.40, P = 0.023 from sepsis, Wilcoxon signed-rank test); no difference was observed between baseline and discharge in patients who did not develop sepsis. Stimulation of PMNs by LPS led to increased expression of aquaporin-1 in vitro, which could be abrogated by the NF-κB inhibitor EF-24. PMN hypotonic challenge resulted in a transient increase of the relative cell volume, which returned to baseline after 600 seconds, while incubation in the presence of LPS resulted in persistently increased cell volume. The latter could be abolished by blocking aquaporin-1 with mercury and restored by incubation in β-mercaptoethanol, which abrogated the action of mercury inhibition.
  
  
  CONCLUSIONS
  Aquaporin-1 is induced in leukocytes of patients with ICU-acquired sepsis and exhibits higher expression in septic shock. This phenomenon may be due to LPS-triggered NF-κB activation that can also lead to alterations in plasma membrane permeability.
authors.forename: Alice G
authors.initials: AG
authors.lastname: Vassiliou
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Maniatis
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Orfanos
authors.forename: Zafeiria
authors.initials: Z
authors.lastname: Mastora
authors.forename: Edison
authors.initials: E
authors.lastname: Jahaj
authors.forename: Triantafillos
authors.initials: T
authors.lastname: Paparountas
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.forename: Charis
authors.initials: C
authors.lastname: Roussos
authors.forename: Vassilis
authors.initials: V
authors.lastname: Aidinis
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kotanidou
mesh_terms: D000328:Adult; D000368:Aged; D051398:Aquaporin 1 / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*
chemical_list: C496020:AQP1 protein, human; D051398:Aquaporin 1
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