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| 34. |
- Wan, Ming Xiu, et al.
(författare)
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Leukocyte rolling is exclusively mediated by P-selectinin colonic venules.
- 2002
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 135:7, s. 1749-1756
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Tidskriftsartikel (refereegranskat)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.
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| 35. |
- Wan, M X, et al.
(författare)
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Protective effect of low molecular weight heparin on experimental colitis: role of neutrophil recruitment and TNF-alpha production.
- 2002
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Ingår i: Inflammation Research. - 1420-908X. ; 51:4, s. 182-187
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to examine the impact and mechanism of action of low molecular weight heparin (LMWH) in a model of murine colitis. MATERIALS AND METHODS: Balb/c mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for five days. LMWH (500 units/kg/day) was administered by subcutaneous injection prior to and throughout the treatment period with DSS. Clinical disease activity index (DAI), including body weight loss, stool consistency and blood in feces were examined daily. Moreover, crypt height (CH), mucosal damage score (MDS), myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-alpha) content in the colon were determined. RESULTS: DSS increased DAI, MDS, MPO activity and TNF-alpha production and decreased CH. Administration of LMWH markedly reduced DAI, MDS and reversed the CH-reduction. Moreover, in LMWH-treated animals, the MPO activity was reduced by more than 67% whereas mucosal levels of TNF-alpha was similar compared to DSS control mice. CONCLUSIONS: These findings suggest that LMWH inhibits murine colitis by interference with neutrophil recruitment and that LMWH may provide a novel pharmacological approach to treatment of inflammatory bowel disease.
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| 38. |
- Zhang, X.W., et al.
(författare)
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Inhibition of selectin function and leukocyte rolling protects against dextran sodium sulfate-induced murine colitis
- 2001
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 36:3, s. 270-275
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Tidskriftsartikel (refereegranskat)abstract
- Background: The selectin family of adhesion molecules (P-, E- and L-selectin) plays an important role in inflammatory reactions by mediating interactions between leukocytes and activated endothelial cells. However, a recent study using gene-targeted mice has suggested that adhesion molecules (P- and E-selectin and ICAM-1) may not be relevant targets in intestinal inflammation. The objective of the present study was to re-evaluate the potential role of selectins in experimental colitis in wild-type mice using the polysaccharide fucoidan, which inhibits the function of P- and L-selectin. Methods: For this purpose, Balb/c mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for 5 days with and without daily administration of fucoidan (25 mg/kg, i.v.). In separate experiments, the effect of fucoidan on leukocyte-endothelium interactions was examined by use of intravital microscopy. Results: It was found that pretreatment with fucoidan (25 mg/kg/day) reduced mucosal damage and crypt destruction in the colon of DSS-treated mice. Moreover, this fucoidan treatment markedly reduced the colonic MPO activity in mice exposed to DSS. In vivo microscopy revealed that the dose of fucoidan used in the present study abolished TNF-alpha -induced venular leukocyte rolling and extravascular recruitment. Conclusions: These results suggest that selectins mediate leukocyte infiltration and tissue damage in experimental colitis. Moreover, our data support: the concept that functional interference with adhesion molecules of the selectin family may have a beneficial effect in the treatment of inflammatory bowel disease.
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