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

Inflamm Res. 2007 May;56(5):189-94. doi: 10.1007/s00011-007-6163-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Chemokine CXCL2
  • Chemokines / metabolism
  • Endotoxemia / chemically induced
  • Endotoxemia / pathology
  • Endotoxemia / physiopathology*
  • Endotoxins
  • Ileum / metabolism
  • Ileum / pathology
  • Ileum / physiopathology*
  • Interleukin-8 / metabolism
  • Intestinal Absorption / drug effects
  • Intestinal Absorption / physiology*
  • Leukocytes / pathology
  • Leukocytes / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • P-Selectin / physiology*

Substances

  • Chemokine CXCL2
  • Chemokines
  • Cxcl2 protein, mouse
  • Endotoxins
  • Interleukin-8
  • P-Selectin