Critical role of P-selectin-dependent leukocyte recruitment in endotoxin-induced intestinal barrier dysfunction in mice.

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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.
Original languageEnglish
Pages (from-to)189-194
JournalInflammation Research
Volume56
Issue number5
DOIs
Publication statusPublished - 2007

Subject classification (UKÄ)

  • Rheumatology and Autoimmunity

Keywords

  • P-selectin
  • leukocyte
  • sepsis
  • intestinal barrier
  • endotoxin

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