HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/1/G115    most recent 00207.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Rijcken, E. M. Articles by Krieglstein, C. F. Search for Related Content PubMed PubMed Citation Articles by Rijcken, E. M. Articles by Krieglstein, C. F.

INFLAMMATION/IMMUNITY/MEDIATORS

Immunoblockade of PSGL-1 attenuates established experimental murine colitis by reduction of leukocyte rolling

¹Department of General Surgery, Muenster University Hospital, Muenster; and ²Institute of Cell Biology, ZMBE, University of Muenster and Max-Planck-Institute of Vascular Biology, D-48149 Muenster, Germany

Submitted 6 May 2003 ; accepted in final form 26 February 2004

Recruitment of circulating leukocytes into the colonic tissue is a key feature of intestinal inflammation. P-selectin glycoprotein ligand-1 (PSGL-1) and very late antigen-4 (VLA-4) are expressed on leukocytes and play an important role in leukocyte-endothelial cell adhesive interactions. We examined the effects of immunoneutralization of PSGL-1 and VLA-4 on leukocyte recruitment in vivo in the development and treatment of experimental colitis. Chronic colitis was induced in balb/c mice by oral administration of dextran sodium sulfate (DSS). Monoclonal antibodies 2PH1 (anti-PSGL-1) and PS/2 (anti-VLA-4) or the combination of both were injected intravenously, and leukocyte adhesion was observed for 60 min in colonic submucosal venules by intravital microscopy (IVM) under isoflurane/N₂O anesthesia. In addition, mice with established colitis were treated by daily intraperitoneal injections of 2PH1, PS/2, or the combination of both over 5 days. Disease activity index (DAI), histology, and myeloperoxidase (MPO) levels were compared with sham-treated DSS controls. We found that 2PH1 reduced the number of rolling leukocytes (148.7 ± 29.8 vs. 36.9 ± 8.7/0.01 mm²/30 s, P < 0.05), whereas leukocyte velocity was increased (24.0 ± 3.6 vs. 127.8 ± 11.7 µm/s, P < 0.05). PS/2 reduced leukocyte rolling to a lesser extent. Leukocyte firm adhesion was not influenced by 2PH1 but was strongly reduced by PS/2 (24.1 ± 2 vs. 4.4 ± 0.9/0.01 mm²/30 s, P < 0.05). Combined application did not cause additional effects on leukocyte adhesion. Treatment of chronic colitis with 2PH1 or PS/2 reduced DAI, mucosal injury, and MPO levels significantly. Combined treatment led to a significantly better reduction of DAI (0.4 ± 0.1 vs. 2.1 ± 0.2 points) and histology (9.7 ± 0.9 vs. 21.4 ± 4.6 points). In conclusion, PSGL-1 and VLA-4 play an important role for leukocyte recruitment during intestinal inflammation. Therapeutic strategies designed to disrupt interactions mediated by PSGL-1 and/or VLA-4 may prove beneficial in treatment of chronic colitis.

P-selectin glycoprotein ligand-1; very late antigen-4; dextran sodium sulfate-colitis; selectins; inflammatory bowel disease

This article has been cited by other articles:

				R. Mennigen, K. Nolte, E. Rijcken, M. Utech, B. Loeffler, N. Senninger, and M. Bruewer Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis Am J Physiol Gastrointest Liver Physiol, May 1, 2009; 296(5): G1140 - G1149. [Abstract] [Full Text] [PDF]

				O. Schreiber, J. Petersson, M. Phillipson, M. Perry, S. Roos, and L. Holm Lactobacillus reuteri prevents colitis by reducing P-selectin-associated leukocyte- and platelet-endothelial cell interactions Am J Physiol Gastrointest Liver Physiol, March 1, 2009; 296(3): G534 - G542. [Abstract] [Full Text] [PDF]

				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]

				E. Rijcken, R. B. Mennigen, S. D. Schaefer, M. G. Laukoetter, C. Anthoni, H.-U. Spiegel, M. Bruewer, N. Senninger, and C. F. Krieglstein PECAM-1 (CD 31) mediates transendothelial leukocyte migration in experimental colitis Am J Physiol Gastrointest Liver Physiol, August 1, 2007; 293(2): G446 - G452. [Abstract] [Full Text] [PDF]

				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]

				M. Mori, J. W. Salter, T. Vowinkel, C. F. Krieglstein, K. Y. Stokes, and D. N. Granger Molecular determinants of the prothrombogenic phenotype assumed by inflamed colonic venules Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G920 - G926. [Abstract] [Full Text] [PDF]