Disruption of P-selectin signaling modulates cell trafficking and results in improved outcomes after mouse warm intestinal ischemia and reperfusion injury

Farmer, Douglas G., Anselmo, Dean, Shen, Xiu Da, Ke, Bibo, Carmody, Ian C., Gao, Feng, Lassman, Charles, McDiarmid, Sue V., Shaw, Grey, Busuttil, Ronald W. and Kupiec-Weglinski, Jerzy W. (2005) Disruption of P-selectin signaling modulates cell trafficking and results in improved outcomes after mouse warm intestinal ischemia and reperfusion injury. Transplantation, 80 6: 828-835. doi:10.1097/01.TP.0000174337.53658.B0


Author Farmer, Douglas G.
Anselmo, Dean
Shen, Xiu Da
Ke, Bibo
Carmody, Ian C.
Gao, Feng
Lassman, Charles
McDiarmid, Sue V.
Shaw, Grey
Busuttil, Ronald W.
Kupiec-Weglinski, Jerzy W.
Title Disruption of P-selectin signaling modulates cell trafficking and results in improved outcomes after mouse warm intestinal ischemia and reperfusion injury
Journal name Transplantation   Check publisher's open access policy
ISSN 0041-1337
1534-6080
Publication date 2005-09-01
Sub-type Article (original research)
DOI 10.1097/01.TP.0000174337.53658.B0
Volume 80
Issue 6
Start page 828
End page 835
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
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.
Keyword intestine
ischemia and reperfusion injury
neutrophil
lymphocyte
P selectin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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