title: Neutrophil-dependent pentraxin-3 and reactive oxygen species production modulate endothelial dysfunction in haemodialysis patients.
abstract: BACKGROUND
  The aim of this study was to investigate neutrophil activation and its role in long pentraxin-3 (PTX3) release and oxidative stress generation during haemodialysis (HD) and to correlate neutrophil PTX3 and oxidant expression with endothelial dysfunction.
  
  
  METHODS
  Forty-seven uraemic patients on stable HD, 12 healthy subjects and 15 patients with congestive heart failure (New York Heart Association classes III and IV) were enrolled. Neutrophil PTX3 protein expression was evaluated by confocal microscopy. l -selectin expression, intracellular PTX3 localization and reactive oxygen species (ROS) generation in human neutrophils were measured by flow cytometry. NADPH-dependent superoxide generation was investigated by chemiluminescence. PTX3 plasma concentrations were measured by ELISA. Endothelial dysfunction was studied by flow-mediated dilation (FMD).
  
  
  RESULTS
  The low baseline levels of FMD significantly improved after HD, but worsened by 24 h. A significant up-regulation of PTX3 protein expression, localized within secondary granules, was detected in neutrophils isolated at 30 and 240 min of HD, along with an increase in l -selectin expression. The up-regulation in intracellular PTX3 in neutrophils was associated with a significant increase in PTX3 plasma concentrations at 240 min. HD increased ROS production and NADPH oxidase activity in neutrophils. In a univariate analysis, pre-treatment with FMD was inversely correlated with PTX3 expression and ROS generation in neutrophils. In a multivariate analysis, both circulating pre-HD PTX3 and intracellular ROS generation by neutrophils were independent predictors of abnormal FMD.
  
  
  CONCLUSIONS
  Neutrophil overexpression of PTX3 is associated with ROS overproduction and endothelial dysfunction and may represent an emerging marker of vascular damage progression in HD patients.
authors.affiliation: Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: dell'Oglio
authors.affiliation: Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Simone
authors.affiliation: Department of Emergency and Organ Transplantation, Cardiology Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ciccone
authors.affiliation: Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Corciulo
authors.affiliation: Department of Emergency and Organ Transplantation, Cardiology Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Gesualdo
authors.affiliation: Department of Emergency and Organ Transplantation, Cardiology Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Annapaola
authors.initials: A
authors.lastname: Zito
authors.affiliation: Department of Emergency and Organ Transplantation, Cardiology Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cortese
authors.affiliation: Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castellano
authors.affiliation: Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Gigante
authors.affiliation: Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.affiliation: Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
authors.affiliation: Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Pertosa
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D006435:Renal Dialysis; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D015854:Up-Regulation; D014652:Vascular Diseases / Q000097:blood / Q000473:pathology*; D000099153:Pentraxins
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D017382:Reactive Oxygen Species; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: endothelial dysfunction; haemodialysis; neutrophils; oxidative stress; pentraxin-3