title: Effect of leptin on polymorphonuclear leucocyte functions in healthy subjects and haemodialysis patients.
abstract: BACKGROUND
  Dysfunction of polymorphonuclear leucocytes (PMNLs) in end-stage renal disease (ESRD) patients contributes to a diminished immune defence. The serum levels of leptin are elevated in patients with ESRD. We analysed in vitro effects of leptin on PMNLs from healthy subjects (HS; n = 12) and haemodialysis (HD) patients (n = 15) before and after HD.
  
  
  METHODS
  PMNL oxidative burst and phagocytosis were tested by flow cytometry in whole blood. Chemotaxis of isolated PMNLs was assessed by the under-agarose method. To assess the involvement of leptin in PMNL signalling pathways, signal transduction inhibitors were used and the activity of intracellular kinases was investigated by western blotting, in vitro kinase assays and the Luminex technology.
  
  
  RESULTS
  Increasing the leptin level in the blood of HS leads to a reduced activation of the oxidative burst by Escherichia coli and phorbol 12-myristate 13-acetate. Activation of the oxidative burst is reduced in the blood of HD patients and the addition of leptin does not lead to further PMNL inhibition. Leptin at a concentration measured in HD patients significantly reduces the chemotaxis of PMNLs from HS but had no effect on PMNLs from ESRD patients before and also after HD treatment with high-flux dialysers. The phosphoinositide 3-kinase/Akt pathway is involved in the inhibitory effects of leptin.
  
  
  CONCLUSIONS
  In the presence of leptin, PMNLs from HS and HD patients respond differently to stimuli. The lack of response to leptin in PMNLs from HD patients cannot be influenced by HD.
authors.affiliation: Department of Internal Medicine, Division of Nephrology and Hypertension, University of Cincinnati, Cincinnati, OH, USA. gerald.cohen@meduniwien.ac.at
authors.forename: Gerald
authors.initials: G
authors.lastname: Cohen
authors.forename: Jana
authors.initials: J
authors.lastname: Raupachova
authors.forename: Dalibor
authors.initials: D
authors.lastname: Ilic
authors.forename: Johannes
authors.initials: J
authors.lastname: Werzowa
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
mesh_terms: D015153:Blotting, Western; D016022:Case-Control Studies; D002633:Chemotaxis; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D020738:Leptin / Q000097:blood*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects*; D010766:Phosphorylation; D011379:Prognosis; D006435:Renal Dialysis; D016897:Respiratory Burst / Q000187:drug effects*; D012307:Risk Factors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D020738:Leptin; D051550:I-kappa B Kinase; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate