Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on November 1, 2004

Published online before print August 17, 2004
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow All Versions of this Article:
jlb.0204110v1
76/5/933    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cuzzocrea, S.
Right arrow Articles by Riccardi, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cuzzocrea, S.
Right arrow Articles by Riccardi, C.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0204110

Received for publication February 24, 2004.
Revised June 3, 2004.
Accepted for publication July 7, 2004.

Article

Glucocorticoid-induced TNF receptor family gene (GITR) knockout mice exhibit a resistance to splanchnic artery occlusion (SAO) shock

Salvatore Cuzzocrea *@, Giuseppe Nocentini {dagger}, Rosanna Di Paola *, Emanuela Mazzon *, Simona Ronchetti {dagger}, Tiziana Genovese *, Carmelo Muià *, Achille P. Caputi *, and Carlo Riccardi {dagger}

*Dipartimento Clinico e Sperimentale di Medicina e Farmacologia, Torre Biologica, Policlinico Universitario, Messina, Italy; and {dagger}Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia, Italy

@ To whom correspondence should be addressed. E-mail: salvator{at}unime.it.


  Abstract

In the present study, we used glucocorticoid-induced tumor necrosis factor (TNF) receptor family gene knockout (GITR-KO) mice to evaluate a possible role of GITR on the pathogenesis of splanchnic artery occlusion (SAO) shock, which was induced in mice by clamping the superior mesenteric artery and the celiac artery for 30 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, animals were killed for histological examination and biochemical studies. There was a marked increase in the lipid peroxidation in the ileum of the SAO-shocked, GITR wild-type (WT) mice after reperfusion. The absence of GITR significantly reduced the lipid peroxidation in the intestine. SAO-shocked WT mice developed a significant increase of ileum tissue, TNF-{alpha}, and myeloperoxidase activity and marked histological injury. SAO shock was also associated with a significant mortality (5% survival at 24 h after reperfusion). Reperfused ileum tissue sections from SAO-shocked WT mice showed positive staining for P-selectin, intercellular adhesion molecule 1 (ICAM-1), and E-selectin. The intensity and degree of P-selectin, E-selectin, and ICAM-1 were markedly reduced in tissue section from SAO-shocked, GITR-KO mice. SAO-shocked, GITR-KO mice also showed a significant reduction of the TNF-{alpha} production and neutrophil infiltration into the reperfused intestine, an improved histological status of the reperfused tissues, and an improved survival. Taken together, our results clearly demonstrate that GITR plays an important role in the ischemia and reperfusion injury and put forward the hypothesis that modulation of GITR expression may represent a novel and possible strategy.

Key Words: adhesion molecules • ischemia and reperfusion • neutrophil infiltration • lipid peroxidation






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2004 by the Society for Leukocyte Biology.