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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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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
The British Pharmacological Society
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
2007-07-30 14:49:40
date last changed
2017-01-01 06:59:43
@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},
  keyword      = {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    = {The British Pharmacological Society},
  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},
  volume       = {135},
  year         = {2002},
}