Abstract.
Objective:
To define the importance of leukocyte recruitment in endotoxin-induced gut permeability.
Materials and methods:
31 male C57BL/6 mice were challenged with lipopolysaccharide (LPS). Ileal permeability was measured in Ussing chambers and leukocyte-endothelium interactions studied with intravital fluorescence microscopy after 18 h.
Results:
LPS caused a clear-cut increase in leukocyte accumulation and intestinal permeability. Immunoneutralisation of P-selectin not only reduced leukocyte recruitment significantly (54 % reduction) but also abolished endotoxin-induced intestinal leakage. Intestinal levels of pro-inflammatory chemokines increased markedly in response to LPS but were not influenced by inhibition of P-selectin in vivo.
Conclusion:
The present study shows not only that endotoxin-induced leukocyte recruitment is mediated by P-selectin but also that sepsis-associated intestinal leakage in the gut is largely regulated by leukocyte accumulation. Thus, our novel data demonstrate a critical link between P-selectin-dependent leukocyte recruitment and gut barrier failure in endotoxemia.
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Received 26 July 2006; returned for revision 24 October 2006; accepted by M. Parnham 8 November 2006.
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Mangell, P., Mihaescu, A., Wang, Y. et al. Critical role of P-selectin-dependent leukocyte recruitment in endotoxin-induced intestinal barrier dysfunction in mice. Inflamm. res. 56, 189–194 (2007). https://doi.org/10.1007/s00011-007-6163-x
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DOI: https://doi.org/10.1007/s00011-007-6163-x