title: In vitro and in vivo models for peritonitis demonstrate unchanged neutrophil migration after exposure to dialysis fluids.
abstract: BACKGROUND
  Recurrent infections in peritoneal dialysis (PD) patients may alter the abdominal wall resulting in an impairment of its dialysis capacity. In this study we investigated both in vitro and in vivo the effects of mesothelial exposure to dialysis fluids on the migration of neutrophils and their capacity to clear a bacterial infection.
  
  
  METHODS
  First, we evaluated neutrophil migration in an in vitro transwell model for the peritoneal membrane with monolayers of primary human mesothelial cells (MC) on the lower side and primary human endothelial cells (EC) on top of the same transwell membrane, upon exposure of MC to PD fluid (PDF)-derived components. In addition to this in vitro model, we combined chronic peritoneal exposure to PDF with a peritoneal infection model in the rat. We investigated the kinetics of the chemokine response, neutrophil recruitment and bacterial clearance.
  
  
  RESULTS
  Known chemoattractants, such as fMLP and IL-8, strongly increased neutrophil migration across both cell layers in the in vitro model of the peritoneal membrane. Pre-incubation of the MC layer for 48 h with 55 mM glucose, a combination of two glucose degradation products, methylglyoxal and 3-deoxyglucosone, or conventional dialysis fluid (1:4 dilution), however, did not change the IL-8-induced migration of neutrophils. In concert with this finding we demonstrated an unchanged MC expression of ICAM-1 and VCAM-1 after these pre-treatments. Unexpectedly, chronic i.p. exposure to conventional PDF or a recently developed lactate/bicarbonate-buffered PDF in a rat peritoneal exposure model strongly hampered the chemokine response upon bacterial challenge. Nevertheless, neutrophil recruitment and bacterial clearance were effective and did not differ from rats not pre-exposed to PDF.
  
  
  CONCLUSIONS
  We conclude that exposure of MC to PDF does not hamper the recruitment of functional neutrophils upon challenge.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, FdG, Postbus 7057, 1007 MB Amsterdam, The Netherlands. j.vandenborn@vumc.nl
authors.forename: Angelique G A
authors.initials: AG
authors.lastname: Welten
authors.forename: Mohammad
authors.initials: M
authors.lastname: Zareie
authors.forename: Jacob
authors.initials: J
authors.lastname: van den Born
authors.forename: Piet M
authors.initials: PM
authors.lastname: ter Wee
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Bas A J
authors.initials: BA
authors.lastname: Driesprong
authors.forename: Frederik P J
authors.initials: FP
authors.lastname: Mul
authors.forename: Peter L
authors.initials: PL
authors.lastname: Hordijk
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Beelen
authors.forename: Liesbeth H P
authors.initials: LH
authors.lastname: Hekking
mesh_terms: D001826:Body Fluids; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells; D004927:Escherichia coli Infections / Q000382:microbiology; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000382:microbiology; D010538:Peritonitis / Q000276:immunology* / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000382:microbiology