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P-selectin knockout mice have improved outcomes with both warm ischemia and small bowel transplantation

2004; Elsevier BV; Volume: 36; Issue: 2 Linguagem: Inglês

10.1016/j.transproceed.2003.12.014

1873-2623

Ian Carmody, Lingzhong Meng, Xiaoxu Shen, Denilson de Sousa Anselmo, Feng Gao, Bibo Ke, Jeffrey Ma, Jerzy W. Kupiec‐Weglinski, Sue V. McDiarmid, Ronald W. Busuttil, Grey Shaw, Douglas G. Farmer,

Transplantation: Methods and Outcomes

To analyze the role of P-selectin in intestinal ischemia and reperfusion injury (IRI) using murine models. 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. 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 7 days in group B, and <72 hours in group C. 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.