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, 2007

Published online before print July 26, 2007
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow All Versions of this Article:
jlb.0207118v1
82/5/1239    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 Buanne, P.
Right arrow Articles by Bertini, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buanne, P.
Right arrow Articles by Bertini, R.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0207118

Received for publication February 19, 2007.
Revised March 28, 2007.
Accepted for publication June 21, 2007.

Article

Crucial pathophysiological role of CXCR2 in experimental ulcerative colitis in mice

Pasquale Buanne *, Emma Di Carlo {dagger}{ddagger}, Lorenzo Caputi *, Laura Brandolini *, Marco Mosca *, Franca Cattani *, Luigi Pellegrini *, Leda Biordi {sect}, Gino Coletti , Carlo Sorrentino {dagger}{ddagger}, Guido Fedele ||, Francesco Colotta *#, Gabriella Melillo *, and Riccardo Bertini *@

*Department of Preclinical Pharmacology, Dompé pha.r.ma s.p.a., L’Aquila, Italy; {dagger}Department of Oncology and Neurosciences, Surgical Pathology Section, "G. d’Annunzio" University, Chieti, Italy; {ddagger}Ce. S.I. Aging Research Center, "G. d’Annunzio" University Foundation, Chieti, Italy; {sect}Experimental Medicine Department, University of L’Aquila, L’Aquila, Italy;¶Operative Unit of Pathological Anatomy, S. Salvatore Regional Hospital, L’Aquila, Italy;||Biometry Unit, Dompé pha.r.ma s.p.a., Milan, Italy; and#Nerviano Medical Sciences, Milan, Italy

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


  Abstract

Polymorphonuclear leukocyte infiltration and activation into colonic mucosa are believed to play a pivotal role in mediating tissue damage in human ulcerative colitis (UC). Ligands of human CXC chemokine receptor 1 and 2 (CXCR1/R2) are chemoattractants of PMN, and high levels were found in the mucosa of UC patients. To investigate the pathophysiological role played by CXCR2 in experimental UC, we induced chronic experimental colitis in WT and CXCR2-/- mice by two consecutive cycles of 4% dextran sulfate sodium administration in drinking water. In wild-type (WT) mice, the chronic relapsing of DSS-induced colitis was characterized by clinical signs and histopathological findings that closely resemble human disease. CXCR2-/- mice failed to show PMN infiltration into the mucosa and, consistently with a key role of PMN in mediating tissue damage in UC, showed limited signs of mucosal damage and reduced clinical symptoms. Our data demonstrate that CXCR2 plays a key pathophysiological role in experimental UC, suggesting that CXCR2 activation may represent a relevant pharmacological target for the design of novel pharmacological treatments in human UC.

Key Words: rodent • neutrophils • inflammation






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2007 by the Society for Leukocyte Biology.