title: Critical role of P-selectin-dependent leukocyte recruitment in endotoxin-induced intestinal barrier dysfunction in mice.
abstract: OBJECTIVE
  To define the importance of leukocyte recruitment in endotoxin-induced gut permeability.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery Malmö University Hospital, Lund University, 205 02, Malmö, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Mangell
authors.forename: A
authors.initials: A
authors.lastname: Mihaescu
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Schramm
authors.forename: B
authors.initials: B
authors.lastname: Jeppsson
authors.forename: H
authors.initials: H
authors.lastname: Thorlacius
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004731:Endotoxins; D007082:Ileum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016209:Interleukin-8 / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007962:Leukocytes / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000502:physiology*
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D004731:Endotoxins; D016209:Interleukin-8; D019007:P-Selectin