title: P-selectin knockout mice have improved outcomes with both warm ischemia and small bowel transplantation.
abstract: OBJECTIVE
  To analyze the role of P-selectin in intestinal ischemia and reperfusion injury (IRI) using murine models.
  
  
  METHODS
  A model of warm IRI wherein the SMA was occluded for 100 minutes was undertaken in the following groups (10 mice per group): Group 1 (control) wild-type (WT) C57BL6, no treatment; Group 2: 0.4 mg/kg of r-PSGL1-lg 10 minutes before and after clamping; Group 3: PSGL KO mice. Survival was assessed at 7 days; the intestine was assayed for histopathology, apoptosis, myeloperoxidase (MPO), IL1, and TNF. A second model of cold IRI followed by intestinal transplantation (IT) was undertaken in the following groups (two mice per group): Group A WT --> WT: Group B PSGL KO --> WT (1-hour ischemia); Group C: PSGL KO --> WT (2 hour ischemia). Survival only was assessed.
  
  
  RESULTS
  Survival was 50% in group 1, 90% in group 2, and 100% in group 3. Graded histopathology and crypt apoptosis demonstrated significantly less injury in groups B and C. MPO was not different between groups. IL1 and TNF were significantly reduce in groups 2 and 3. Following IT, survival was <12 hours in group A, >7 days in group B, and <72 hours in group C.
  
  
  CONCLUSIONS
  This study clearly demonstrates the importance of P-selectin in warm and cold IRI in that the blockade of P-selectin using rPSGL1-lg or the absence of P-selectin using KO mice confers a survival advantage and reduction in tissue injury. The mechanism is unclear but appears to be independent of neutrophil infiltration.
authors.affiliation: Dumont-UCLA Transplant Program, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: I C
authors.initials: IC
authors.lastname: Carmody
authors.forename: L
authors.initials: L
authors.lastname: Meng
authors.forename: X D
authors.initials: XD
authors.lastname: Shen
authors.forename: D
authors.initials: D
authors.lastname: Anselmo
authors.forename: F
authors.initials: F
authors.lastname: Gao
authors.forename: B
authors.initials: B
authors.lastname: Ke
authors.forename: J P
authors.initials: JP
authors.lastname: Ma
authors.forename: J W
authors.initials: JW
authors.lastname: Kupiec-Weglinski
authors.forename: S V
authors.initials: SV
authors.lastname: McDiarmid
authors.forename: R W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: G
authors.initials: G
authors.lastname: Shaw
authors.forename: D G
authors.initials: DG
authors.lastname: Farmer
mesh_terms: D000818:Animals; D007421:Intestine, Small / Q000098:blood supply / Q000473:pathology / Q000637:transplantation*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D015427:Reperfusion Injury; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D019007:P-Selectin