The Journal of Experimental Medicine
Rockland Immunochemicals for Research
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 27 February 2006 doi:10.1084/jem.20050407
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 3, 541-552
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2498K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Olson, T. S.
Right arrow Articles by Pizarro, T. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Olson, T. S.
Right arrow Articles by Pizarro, T. T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 The primary defect in experimental ileitis originates from a nonhematopoietic source

Timothy S. Olson1,3, Brian K. Reuter2, Kevin G-E. Scott2, Margaret A. Morris3,4, Xiao-Ming Wang2, Leslie N. Hancock2, Tracy L. Burcin3,4, Steven M. Cohn2, Peter B. Ernst2, Fabio Cominelli2, Jonathan B. Meddings5, Klaus Ley3,4, and Theresa T. Pizarro2

1 Department of Molecular Physiology, 2 Digestive Health Center of Excellence, 3 Robert M. Berne Cardiovascular Research Center, and 4 Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, VA 22908 5 Department of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2B7

CORRESPONDENCE Theresa T. Pizarro: ttp4e{at}virginia.edu

The initiating etiologic factor in Crohn's disease (CD) remains unclear. SAMP1/YitFc (SAMP) mice develop chronic ileitis similar to human CD. We used bone marrow chimeras to determine if SAMP ileitis results from a primary immunological defect or from dysregulated mucosal immunity secondary to intrinsic, nonhematopoietic (e.g., epithelial) dysfunction. SAMP mice receiving wild-type (AKR) BM developed severe ileitis, whereas SAMP BM did not confer ileitis to WT recipients. WT lymphocytes from reconstituted SAMP mice resembled native SAMP populations in regard to surface phenotype and cytokine production. Ilea from native SAMP mice and SAMP recipients of wild-type BM displayed decreased epithelial barrier resistance ex vivo and increased epithelial permeability in vivo compared to native WT mice and AKR recipients of SAMP BM. This permeability defect preceded the development of ileal inflammation, was present in the absence of commensal bacteria, and was accompanied by altered ileal mRNA expression of the tight junction proteins claudin-2 and occludin. Our results provide evidence that the primary defect conferring ileitis in SAMP mice originates from a nonhematopoietic source. Generation of pathogenic lymphocytes is a consequence of this defect and does not reflect intrinsic proinflammatory leukocyte properties. Decreased barrier function suggests that defects in the epithelium may represent the primary source of SAMP ileitis susceptibility.

Abbreviations used: BMT, bone marrow transplant; CD, Crohn's disease; CLDN, claudin; FE, fractional excretion; GF, germ-free; HGPRT, hypoxanthine-guanine phosphoribosyl transferase; MLN, mesenteric lymph node; MPO, myeloperoxidase; SAMP, SAMP1/YitFc; SPF, specific pathogen-free; TEER, transepithelial electrical resistance; TJ, tight junction.

T.S. Olson and B.K. Reuter contributed equally to this work.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS