P-selectin knockout mice have improved outcomes with both warm ischemia and small bowel transplantation.
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.
Carmody
I C
IC
Dumont-UCLA Transplant Program, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Meng
L
L
Shen
X D
XD
Anselmo
D
D
Gao
F
F
Ke
B
B
Ma
J P
JP
Kupiec-Weglinski
J W
JW
McDiarmid
S V
SV
Busuttil
R W
RW
Shaw
G
G
Farmer
D G
DG
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
D019007:P-Selectin