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.
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 HDpatients and the addition of leptin does not lead to further PMNL inhibition. Leptin at a concentration measured in HDpatients significantly reduces the chemotaxis of PMNLs from HS but had no effect on PMNLs from ESRDpatients 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 HDpatients respond differently to stimuli. The lack of response to leptin in PMNLs from HDpatients cannot be influenced by HD.
Authors: Raymond Vanholder; Rita De Smet; Griet Glorieux; Angel Argilés; Ulrich Baurmeister; Philippe Brunet; William Clark; Gerald Cohen; Peter Paul De Deyn; Reinhold Deppisch; Beatrice Descamps-Latscha; Thomas Henle; Achim Jörres; Horst Dieter Lemke; Ziad A Massy; Jutta Passlick-Deetjen; Mariano Rodriguez; Bernd Stegmayr; Peter Stenvinkel; Ciro Tetta; Christoph Wanner; Walter Zidek Journal: Kidney Int Date: 2003-05 Impact factor: 10.612
Authors: Eva Schepers; Erica Houthuys; Annemieke Dhondt; Grim De Meyer; Nathalie Neirynck; Pascale Bernaert; Rafael Van den Bergh; Peter Brouckaert; Raymond Vanholder; Griet Glorieux Journal: PLoS One Date: 2015-04-01 Impact factor: 3.240