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Protein-bound uremic toxins stimulate crosstalk between leukocytes and vessel wall

Anneleen Pletinck UGent, Griet Glorieux UGent, Eva Schepers, Gerald Cohen, Bertrand Gondouin, Maria Van Landschoot, Sunny Eloot UGent, Angelique Rops, Johan Van de Voorde UGent, An De Vriese, et al. (2013) JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY. 24(12). p.1981-1994
abstract
Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
FREE P-CRESOL, CHRONIC-RENAL-FAILURE, INDOXYL SULFATE, HEMODIALYSIS-PATIENTS, HEPARAN-SULFATE, CARDIOVASCULAR-DISEASE, OXIDATIVE STRESS, IN-VIVO, GLOMERULAR ENDOTHELIAL-CELLS, CHRONIC KIDNEY-DISEASE
journal title
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
J. Am. Soc. Nephrol.
volume
24
issue
12
pages
1981 - 1994
Web of Science type
Article
Web of Science id
000328817300009
JCR category
UROLOGY & NEPHROLOGY
JCR impact factor
9.466 (2013)
JCR rank
2/77 (2013)
JCR quartile
1 (2013)
ISSN
1046-6673
DOI
10.1681/ASN.2012030281
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
4267941
handle
http://hdl.handle.net/1854/LU-4267941
date created
2014-02-06 14:16:16
date last changed
2016-12-19 15:44:56
@article{4267941,
  abstract     = {Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.},
  author       = {Pletinck, Anneleen and Glorieux, Griet and Schepers, Eva and Cohen, Gerald and Gondouin, Bertrand and Van Landschoot, Maria and Eloot, Sunny and Rops, Angelique and Van de Voorde, Johan and De Vriese, An and van der Vlag, Johan and Brunet, Philippe and Van Biesen, Wim and Vanholder, Raymond},
  issn         = {1046-6673},
  journal      = {JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY},
  keyword      = {FREE P-CRESOL,CHRONIC-RENAL-FAILURE,INDOXYL SULFATE,HEMODIALYSIS-PATIENTS,HEPARAN-SULFATE,CARDIOVASCULAR-DISEASE,OXIDATIVE STRESS,IN-VIVO,GLOMERULAR ENDOTHELIAL-CELLS,CHRONIC KIDNEY-DISEASE},
  language     = {eng},
  number       = {12},
  pages        = {1981--1994},
  title        = {Protein-bound uremic toxins stimulate crosstalk between leukocytes and vessel wall},
  url          = {http://dx.doi.org/10.1681/ASN.2012030281},
  volume       = {24},
  year         = {2013},
}

Chicago
Pletinck, Anneleen, Griet Glorieux, Eva Schepers, Gerald Cohen, Bertrand Gondouin, MARIA VAN LANDSCHOOT, Sunny Eloot, et al. 2013. “Protein-bound Uremic Toxins Stimulate Crosstalk Between Leukocytes and Vessel Wall.” Journal of the American Society of Nephrology 24 (12): 1981–1994.
APA
Pletinck, A., Glorieux, G., Schepers, E., Cohen, G., Gondouin, B., VAN LANDSCHOOT, M., Eloot, S., et al. (2013). Protein-bound uremic toxins stimulate crosstalk between leukocytes and vessel wall. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 24(12), 1981–1994.
Vancouver
1.
Pletinck A, Glorieux G, Schepers E, Cohen G, Gondouin B, VAN LANDSCHOOT M, et al. Protein-bound uremic toxins stimulate crosstalk between leukocytes and vessel wall. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY. 2013;24(12):1981–94.
MLA
Pletinck, Anneleen, Griet Glorieux, Eva Schepers, et al. “Protein-bound Uremic Toxins Stimulate Crosstalk Between Leukocytes and Vessel Wall.” JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 24.12 (2013): 1981–1994. Print.