title: Disruption of P-selectin signaling modulates cell trafficking and results in improved outcomes after mouse warm intestinal ischemia and reperfusion injury.
abstract: BACKGROUND
  This study analyzes the role of T lymphocytes and neutrophils (PMN) in intestinal ischemia and reperfusion injury (IRI) using either P-selectin blockade or elimination.
  
  
  METHODS
  Using a model of severe mouse warm intestinal IRI, the following groups were performed: group 1: wild type C57BL6 no treatment; group 2: wild type treated with r-PSGL1-Ig; group 3: C57BL6 genetically deficient in P-selectin. Survival was assessed at day 7; intestine was assayed for histopathology, apoptosis, myeloperoxidase (MPO), inflammatory cytokines, hemoxygenase-1 (HO-1), and CD3 lymphocytes. Standard statistical comparison was undertaken.
  
  
  RESULTS
  The survival was significantly (P < 0.01) improved in the treatment groups: group 1, 50%; group 2, 90%; group 3, 100%. Graded histopathology and crypt apoptosis were improved in groups 2 and 3. MPO and CD3 positive cells were significantly reduced in groups 2 and 3. A significant reduction in inflammatory/Th1-type cytokines was seen in groups 2 and 3 as compared to group 1. Conversely, a significant increase in Th2-type cytokines and HO-1 production was seen selectively in groups 2 and 3.
  
  
  CONCLUSIONS
  This study demonstrates the importance of P-selectin signaling in warm, murine intestinal IRI in that either the blockade of or the genetic deficiency in P-selectin confers a survival advantage and reduction in tissue injury/inflammation. The mechanism involves a reduction of PMN and CD3 T cell infiltration and an alteration in the cytokine microenvironment in favor of a Th2 profile. These data implicate T lymphocyte as an important regulatory cell in this inflammatory process.
authors.affiliation: Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7054, USA. dgfarmer@mednet.ucla.edu
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Farmer
authors.forename: Dean
authors.initials: D
authors.lastname: Anselmo
authors.forename: Xiu
authors.initials: X
authors.lastname: Da Shen
authors.forename: Bibo
authors.initials: B
authors.lastname: Ke
authors.forename: Ian C
authors.initials: IC
authors.lastname: Carmody
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Charles
authors.initials: C
authors.lastname: Lassman
authors.forename: Sue V
authors.initials: SV
authors.lastname: McDiarmid
authors.forename: Grey
authors.initials: G
authors.lastname: Shaw
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: Jerzy W
authors.initials: JW
authors.lastname: Kupiec-Weglinski
mesh_terms: D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex / Q000378:metabolism; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology* / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D021381:Protein Transport; D015427:Reperfusion Injury / Q000503:physiopathology*; D015398:Signal Transduction; D015996:Survival Rate; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D016896:Treatment Outcome; D052096:Warm Ischemia
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D019007:P-Selectin; D009195:Peroxidase; D051547:Heme Oxygenase-1