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Updated: Sep 30, 2026
Murine Colitis Modeling using Dextran Sulfate Sodium (DSS)
Published on: January 19, 2010
The role of P-selectin in experimental colitis as determined by antibody immunoblockade and genetically deficient
Meritxell Gironella1, Meritxell Mollà, Azucena Salas
1Department of Gastroenterology, Institut de Malalties Digestives, IIBB-CSIC, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Villaroel 170, 08036 Barcelona, Spain.
Abstract:
We assessed the effects of genetic ablation of the P-selectin gene in comparison with functional immunoblockade of P-selectin on leukocyte recruitment and the course of disease in dextran sulfate sodium-induced colitis in mice. Compared with control antibody-treated wild-type (WT) mice, WT mice treated with anti-P-selectin antibody and P-selectin(-/-) mice had significantly decreased leukocyte rolling and adhesion in colonic venules and reduced clinical and pathological colitis scores. These reductions were more pronounced in anti-P-selectin-treated than in P-selectin(-/-) mice. In colonic endothelium, up-regulation of ICAM-1 was similar in WT and P-selectin(-/-) mice, but VCAM-1 up-regulation was significantly higher in the latter group. Lung leukocyte infiltration and VCAM-1 expression were increased only in P-selectin(-/-) colitic mice. Mortality was observed only in P-selectin(-/-) mice. Therefore, ablation of P-selectin function ameliorates colitis, but this protection is attenuated in P-selectin(-/-) mice, probably due to compensatory mechanisms that involve up-regulation of other adhesion molecules such as VCAM-1.
Insights
Blocking P-selectin function ameliorates colitis in mice. However, genetic P-selectin deficiency showed reduced protection compared to antibody blockade, suggesting compensatory mechanisms.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Inflammatory bowel disease, such as colitis, involves complex leukocyte recruitment pathways.
- P-selectin plays a crucial role in mediating leukocyte adhesion and migration during inflammation.
Purpose of the Study:
- To compare the therapeutic effects of genetic P-selectin ablation versus P-selectin immunoblockade on dextran sulfate sodium-induced colitis.
- To investigate the role of P-selectin in leukocyte recruitment and disease severity in a murine colitis model.
Main Methods:
- Induction of colitis using dextran sulfate sodium in wild-type (WT) mice and P-selectin-deficient (P-selectin(-/-)) mice.
- Treatment groups included WT mice with control antibody, WT mice with anti-P-selectin antibody, and P-selectin(-/-) mice.
- Assessment of leukocyte rolling and adhesion in colonic venules, clinical and pathological colitis scores, ICAM-1 and VCAM-1 expression, and mortality.
Main Results:
- Both anti-P-selectin antibody treatment and genetic P-selectin deficiency significantly reduced leukocyte recruitment and colitis severity compared to controls.
- The protective effects were more pronounced in anti-P-selectin antibody-treated mice than in P-selectin(-/-) mice.
- P-selectin(-/-) mice exhibited increased VCAM-1 expression and lung leukocyte infiltration, alongside higher mortality, suggesting compensatory mechanisms.
Conclusions:
- P-selectin blockade effectively ameliorates colitis, but genetic ablation shows attenuated protection.
- Compensatory upregulation of other adhesion molecules, like VCAM-1, may limit the therapeutic benefit of complete P-selectin deficiency.
- Targeting P-selectin remains a viable strategy for managing inflammatory conditions like colitis.
