Peritoneal dialysis fluid bioincompatibility and new vessel formation promote leukocyte-endothelium interactions in a chronic rat model for peritoneal dialysis.
Peritoneal dialysis (PD)-induced peritonitis leads to dysfunction of the peritoneal membrane. During peritonitis, neutrophils are recruited to the inflammation site by rolling along the endothelium, adhesion, and transmigration through vessel walls. In a rat PD-model, long-term effects of PD-fluids (PDF) on leukocyte-endothelium interactions and neutrophil migration were studied under baseline and inflammatory conditions. Rats received daily conventional-lactate-buffered PDF (Dianeal), bicarbonate/lactate-buffered PDF (Physioneal) or bicarbonate/lactate buffer (Buffer) during five weeks. Untreated rats served as control. Baseline leukocyte rolling and N-formylmethionyl-leucyl-phenylalanine (fMLP) induced levels of transmigration in the mesentery were evaluated and quantified by intra-vital videomicroscopy and immunohistochemistry. Baseline leukocyte rolling was unaffected by buffer treatment, approximately 2-fold increased after Physioneal and 4-7-fold after Dianeal treatment. After starting fMLP superfusion, transmigrated leukocytes appeared outside the venules firstly after Dianeal treatment (15 minutes), thereafter in Physioneal and Buffer groups (20-22 minutes), and finally in control rats (>25 minutes). Newly formed vessels and total number of transmigrated neutrophils were highest in Dianeal-treated animals, followed by Physioneal and Buffer, and lowest in control rats and correlated for all groups to baseline leukocyte rolling (r = 0.78, P < 0.003). This study indicates that the start of inflammatory neutrophil transmigration is related to PDF bio(in)compatibility, whereas over time neutrophil transmigration is determined by the degree of neo-angiogenesis.
Departments of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. m.schilte@vumc.nl
Margot N
MN
Schilte
Paolo
P
Fabbrini
Piet M Ter
PM
Wee
Eelco D
ED
Keuning
Mohammad
M
Zareie
Geert-Jan
GJ
Tangelder
Anton A
AA
Van Lambalgen
Robert H J
RH
Beelen
Jacob
J
Van Den Born
D000818:Animals; D015314:Dialysis Solutions / Q000009:adverse effects*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D010538:Peritonitis / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D015314:Dialysis Solutions; D009240:N-Formylmethionine Leucyl-Phenylalanine