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Leukocyte rolling is exclusively mediated by P-selectinin colonic venules.

Wan, Ming Xiu ; Riaz, Amjid Ali ; Schramm, Rene ; Wang, Yusheng LU ; Vestweber, Dietmar ; Menger, Michael D and Thorlacius, Henrik LU (2002) In British Journal of Pharmacology 135(7). p.1749-1756
Abstract
1. The objective of the present study was to examine the role of the endothelial selectins (i.e. P- and E-selectin) in leukocyte-endothelium interactions in colonic venules by use of intravital microscopy. 2. Balb/c mice were exposed to dextran sodium sulphate (DSS) in the drinking water for 5 days or treated intraperitoneally (i.p.) with tumour necrosis factor-alpha (TNF-alpha) for 3 h. 3. In DSS-treated mice, mRNA of both P- and E-selectin were expressed and leukocyte rolling and adhesion was increased to 27+/-3 cells min(-1) and 36+/-8 cells mm(-1), respectively. An anti-P-selectin antibody abolished DSS-induced leukocyte rolling, whereas an antibody against E-selectin had no effect. Established leukocyte adhesion was insensitive to... (More)
1. The objective of the present study was to examine the role of the endothelial selectins (i.e. P- and E-selectin) in leukocyte-endothelium interactions in colonic venules by use of intravital microscopy. 2. Balb/c mice were exposed to dextran sodium sulphate (DSS) in the drinking water for 5 days or treated intraperitoneally (i.p.) with tumour necrosis factor-alpha (TNF-alpha) for 3 h. 3. In DSS-treated mice, mRNA of both P- and E-selectin were expressed and leukocyte rolling and adhesion was increased to 27+/-3 cells min(-1) and 36+/-8 cells mm(-1), respectively. An anti-P-selectin antibody abolished DSS-induced leukocyte rolling, whereas an antibody against E-selectin had no effect. Established leukocyte adhesion was insensitive to inhibition of the selectins. 4. DSS markedly increased production of TNF-alpha in the colon. TNF-alpha increased leukocyte rolling to 22+/-3 cells min(-1) and adhesion to 45+/-4 cells mm(-1). Only inhibition of P-selectin significantly reduced (>94%) leukocyte rolling provoked by TNF-alpha. Leukocyte adhesion was not changed by late anti-P-selectin antibody treatment. In contrast, pretreatment with the anti-P-selectin antibody not only abolished leukocyte rolling but also completely inhibited firm adhesion in response to TNF-alpha. 5. This study demonstrates that P-selectin plays an important role in leukocyte rolling in colonic venules, both in experimental colitis and when stimulated with TNF-alpha. Moreover, P-selectin-dependent leukocyte rolling was found to be a precondition for TNF-alpha-induced firm adhesion. Thus, these findings suggest that P-selectin may be a key target to reduce pathological recruitment of inflammatory cells in the colon. (Less)
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organization
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Contribution to journal
publication status
published
subject
keywords
Dextran Sulfate : pharmacology, Animal, Disease Models, E-Selectin : genetics, E-Selectin : metabolism, E-Selectin : physiology, Leukocytes : drug effects, Leukocytes : physiology, Male, Mice, Inbred BALB C, P-Selectin : genetics, P-Selectin : metabolism, RNA, P-Selectin : physiology, Messenger : metabolism, Support, Non-U.S. Gov't, Tumor Necrosis Factor : pharmacology, Venules : cytology, Venules : physiology, Colitis : pathology, Colitis : chemically induced, Cell Adhesion : physiology
in
British Journal of Pharmacology
volume
135
issue
7
pages
1749 - 1756
publisher
Wiley
external identifiers
  • pmid:11934816
  • wos:000174940800020
  • scopus:0036546118
ISSN
1476-5381
DOI
10.1038/sj.bjp.0704638
language
English
LU publication?
yes
id
3b3293af-f5ae-4654-b3fa-425e5fe95764 (old id 107418)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11934816&dopt=Abstract
date added to LUP
2016-04-01 16:14:32
date last changed
2022-02-05 06:49:32
@article{3b3293af-f5ae-4654-b3fa-425e5fe95764,
  abstract     = {{1. The objective of the present study was to examine the role of the endothelial selectins (i.e. P- and E-selectin) in leukocyte-endothelium interactions in colonic venules by use of intravital microscopy. 2. Balb/c mice were exposed to dextran sodium sulphate (DSS) in the drinking water for 5 days or treated intraperitoneally (i.p.) with tumour necrosis factor-alpha (TNF-alpha) for 3 h. 3. In DSS-treated mice, mRNA of both P- and E-selectin were expressed and leukocyte rolling and adhesion was increased to 27+/-3 cells min(-1) and 36+/-8 cells mm(-1), respectively. An anti-P-selectin antibody abolished DSS-induced leukocyte rolling, whereas an antibody against E-selectin had no effect. Established leukocyte adhesion was insensitive to inhibition of the selectins. 4. DSS markedly increased production of TNF-alpha in the colon. TNF-alpha increased leukocyte rolling to 22+/-3 cells min(-1) and adhesion to 45+/-4 cells mm(-1). Only inhibition of P-selectin significantly reduced (>94%) leukocyte rolling provoked by TNF-alpha. Leukocyte adhesion was not changed by late anti-P-selectin antibody treatment. In contrast, pretreatment with the anti-P-selectin antibody not only abolished leukocyte rolling but also completely inhibited firm adhesion in response to TNF-alpha. 5. This study demonstrates that P-selectin plays an important role in leukocyte rolling in colonic venules, both in experimental colitis and when stimulated with TNF-alpha. Moreover, P-selectin-dependent leukocyte rolling was found to be a precondition for TNF-alpha-induced firm adhesion. Thus, these findings suggest that P-selectin may be a key target to reduce pathological recruitment of inflammatory cells in the colon.}},
  author       = {{Wan, Ming Xiu and Riaz, Amjid Ali and Schramm, Rene and Wang, Yusheng and Vestweber, Dietmar and Menger, Michael D and Thorlacius, Henrik}},
  issn         = {{1476-5381}},
  keywords     = {{Dextran Sulfate : pharmacology; Animal; Disease Models; E-Selectin : genetics; E-Selectin : metabolism; E-Selectin : physiology; Leukocytes : drug effects; Leukocytes : physiology; Male; Mice; Inbred BALB C; P-Selectin : genetics; P-Selectin : metabolism; RNA; P-Selectin : physiology; Messenger : metabolism; Support; Non-U.S. Gov't; Tumor Necrosis Factor : pharmacology; Venules : cytology; Venules : physiology; Colitis : pathology; Colitis : chemically induced; Cell Adhesion : physiology}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1749--1756}},
  publisher    = {{Wiley}},
  series       = {{British Journal of Pharmacology}},
  title        = {{Leukocyte rolling is exclusively mediated by P-selectinin colonic venules.}},
  url          = {{http://dx.doi.org/10.1038/sj.bjp.0704638}},
  doi          = {{10.1038/sj.bjp.0704638}},
  volume       = {{135}},
  year         = {{2002}},
}