Advanced

Inhibition of selectin function and leukocyte rolling protects against dextran sodium sulfate-induced murine colitis

Zhang, X.W.; Liu, Qing LU and Thorlacius, Henrik LU (2001) In Scandinavian Journal of Gastroenterology 36(3). p.270-275
Abstract
Background: The selectin family of adhesion molecules (P-, E- and L-selectin) plays an important role in inflammatory reactions by mediating interactions between leukocytes and activated endothelial cells. However, a recent study using gene-targeted mice has suggested that adhesion molecules (P- and E-selectin and ICAM-1) may not be relevant targets in intestinal inflammation. The objective of the present study was to re-evaluate the potential role of selectins in experimental colitis in wild-type mice using the polysaccharide fucoidan, which inhibits the function of P- and L-selectin. Methods: For this purpose, Balb/c mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for 5 days with and without daily... (More)
Background: The selectin family of adhesion molecules (P-, E- and L-selectin) plays an important role in inflammatory reactions by mediating interactions between leukocytes and activated endothelial cells. However, a recent study using gene-targeted mice has suggested that adhesion molecules (P- and E-selectin and ICAM-1) may not be relevant targets in intestinal inflammation. The objective of the present study was to re-evaluate the potential role of selectins in experimental colitis in wild-type mice using the polysaccharide fucoidan, which inhibits the function of P- and L-selectin. Methods: For this purpose, Balb/c mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for 5 days with and without daily administration of fucoidan (25 mg/kg, i.v.). In separate experiments, the effect of fucoidan on leukocyte-endothelium interactions was examined by use of intravital microscopy. Results: It was found that pretreatment with fucoidan (25 mg/kg/day) reduced mucosal damage and crypt destruction in the colon of DSS-treated mice. Moreover, this fucoidan treatment markedly reduced the colonic MPO activity in mice exposed to DSS. In vivo microscopy revealed that the dose of fucoidan used in the present study abolished TNF-alpha -induced venular leukocyte rolling and extravascular recruitment. Conclusions: These results suggest that selectins mediate leukocyte infiltration and tissue damage in experimental colitis. Moreover, our data support: the concept that functional interference with adhesion molecules of the selectin family may have a beneficial effect in the treatment of inflammatory bowel disease. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Tnf-ALPHA, Selectins, Leukocyte, Inflammation, Colitis
in
Scandinavian Journal of Gastroenterology
volume
36
issue
3
pages
270 - 275
publisher
Taylor & Francis
external identifiers
  • wos:000167281900009
  • scopus:0035087025
ISSN
1502-7708
DOI
10.1080/00365520120261
language
English
LU publication?
yes
id
3a27f837-eccb-4938-be65-a7776cb451a2 (old id 1119492)
date added to LUP
2008-07-18 16:31:01
date last changed
2018-05-29 10:34:31
@article{3a27f837-eccb-4938-be65-a7776cb451a2,
  abstract     = {Background: The selectin family of adhesion molecules (P-, E- and L-selectin) plays an important role in inflammatory reactions by mediating interactions between leukocytes and activated endothelial cells. However, a recent study using gene-targeted mice has suggested that adhesion molecules (P- and E-selectin and ICAM-1) may not be relevant targets in intestinal inflammation. The objective of the present study was to re-evaluate the potential role of selectins in experimental colitis in wild-type mice using the polysaccharide fucoidan, which inhibits the function of P- and L-selectin. Methods: For this purpose, Balb/c mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for 5 days with and without daily administration of fucoidan (25 mg/kg, i.v.). In separate experiments, the effect of fucoidan on leukocyte-endothelium interactions was examined by use of intravital microscopy. Results: It was found that pretreatment with fucoidan (25 mg/kg/day) reduced mucosal damage and crypt destruction in the colon of DSS-treated mice. Moreover, this fucoidan treatment markedly reduced the colonic MPO activity in mice exposed to DSS. In vivo microscopy revealed that the dose of fucoidan used in the present study abolished TNF-alpha -induced venular leukocyte rolling and extravascular recruitment. Conclusions: These results suggest that selectins mediate leukocyte infiltration and tissue damage in experimental colitis. Moreover, our data support: the concept that functional interference with adhesion molecules of the selectin family may have a beneficial effect in the treatment of inflammatory bowel disease.},
  author       = {Zhang, X.W. and Liu, Qing and Thorlacius, Henrik},
  issn         = {1502-7708},
  keyword      = {Tnf-ALPHA,Selectins,Leukocyte,Inflammation,Colitis},
  language     = {eng},
  number       = {3},
  pages        = {270--275},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Journal of Gastroenterology},
  title        = {Inhibition of selectin function and leukocyte rolling protects against dextran sodium sulfate-induced murine colitis},
  url          = {http://dx.doi.org/10.1080/00365520120261},
  volume       = {36},
  year         = {2001},
}