Leukocyte rolling is exclusively mediated by P-selectinin colonic venules.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/107418
- author
- Wan, Ming Xiu ; Riaz, Amjid Ali ; Schramm, Rene ; Wang, Yusheng LU ; Vestweber, Dietmar ; Menger, Michael D and Thorlacius, Henrik LU
- organization
- publishing date
- 2002
- type
- 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}}, }