AJP - GI Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol (November 18, 2004). doi:10.1152/ajpgi.00371.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/5/G920    most recent
00371.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mori, M.
Right arrow Articles by Granger, D. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mori, M.
Right arrow Articles by Granger, D. N.
Submitted on August 15, 2004
Accepted on November 15, 2004

Molecular Determinants of the Prothrombogenic Phenotype Assumed by Inflamed Colonic Venules

Mikiji Mori1, James W. Salter1, Thorsten Vowinkel2, Christian F. Krieglstein3, Karen Y. Stokes1, and D. Neil Granger1*

1 Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
2 Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Department of General Surgery, University Hospital Munster, Muenster, Germany
3 Department of General Surgery, University Hospital Munster, Muenster, Germany

* To whom correspondence should be addressed. E-mail: dgrang{at}lsuhsc.edu.

Although platelets have been implicated in the pathogenesis of human inflammatory bowel diseases (IBD), little is known about the magnitude of platelet accumulation in the inflamed bowel, what regulates this process, and its relevance to the overall inflammatory response. In this study, intravital video microscopy was used to monitor the trafficking of platelets and leukocytes, and vascular permeability in colonic venules during the development of colonic inflammation induced by 3% dextran sodium sulfate (DSS). Blocking antibodies directed against different adhesion molecules as well as P-selectin deficient mice were used to define the adhesive determinants of DSS-induced platelet recruitment. DSS induced an accumulation of adherent platelets that was temporally correlated with the appearance of adherent leukocytes and with disease severity. Platelet adhesion, and to a lesser extent leukocyte adhesion, were attenuated by immunoblockade of P-selectin and its ligand P-selectin glycoprotein ligand-1 (PSGL-1), with contributions from both platelet- and endothelial cell-associated P-selectin. DSS induced a rapid and sustained increase in vascular permeability that was greatly attenuated in P-selectin deficient mice. P-selectin bone marrow chimeras revealed that both endothelial cell- and platelet-associated P-selectin contribute to the P-selectin expression detected in the inflamed colonic microvasculature, with endothelial P-selectin making a larger contribution. Our findings indicate that colonic inflammation is associated with the induction of a prothrombogenic phenotype in the colonic microcirculation, with P-selectin and its ligand PSGL-1 playing a major role in the recruitment of platelets.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
L. Deban, C. Correale, S. Vetrano, A. Malesci, and S. Danese
Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades
Am. J. Pathol., June 1, 2008; 172(6): 1457 - 1466.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
T. Vowinkel, K. C. Wood, K. Y. Stokes, J. Russell, A. Tailor, C. Anthoni, N. Senninger, C. F. Krieglstein, and D. N. Granger
Mechanisms of platelet and leukocyte recruitment in experimental colitis
Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G1054 - G1060.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
C. Anthoni, J. Russell, K. C. Wood, K. Y. Stokes, T. Vowinkel, D. Kirchhofer, and D. N. Granger
Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis
J. Exp. Med., July 9, 2007; 204(7): 1595 - 1601.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
W. C. Aird
Phenotypic Heterogeneity of the Endothelium: II. Representative Vascular Beds
Circ. Res., February 2, 2007; 100(2): 174 - 190.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
C. Anthoni, M. G. Laukoetter, E. Rijcken, T. Vowinkel, R. Mennigen, S. Muller, N. Senninger, J. Russell, J. Jauch, J. Bergmann, et al.
Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis
Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1131 - G1137.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
J. Rivera-Nieves, T. L. Burcin, T. S. Olson, M. A. Morris, M. McDuffie, F. Cominelli, and K. Ley
Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis
J. Exp. Med., April 17, 2006; 203(4): 907 - 917.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Mori, K. Y. Stokes, T. Vowinkel, N. Watanabe, J. W. Elrod, N. R. Harris, D. J. Lefer, T. Hibi, and D. N. Granger
Colonic blood flow responses in experimental colitis: time course and underlying mechanisms
Am J Physiol Gastrointest Liver Physiol, December 1, 2005; 289(6): G1024 - G1029.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.