Skip Navigation LinksHome > December 2011 - Volume 53 - Issue 6 > Critical Role for P-Glycoprotein Expression in Hematopoietic...
Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e31822860f1
Original Articles: Gastroenterology

Critical Role for P-Glycoprotein Expression in Hematopoietic Cells in the FVB.Mdr1a−/− Model of Colitis

Staley, Elizabeth M.*; Dimmitt, Reed A.; Schoeb, Trenton R.; Tanner, Scott M.§; Lorenz, Robin G.§

Collapse Box

Abstract

Objective: P-glycoprotein (P-gp), the functional product of the multidrug resistance gene (MDR), is a transmembrane protein that extrudes substrates from the intracellular environment. P-gp is expressed on the apical surface of epithelial cells and on cells from the hematopoietic lineage. Human MDR polymorphisms have been associated with the increased risk of inflammatory bowel disease, and FVB/N animals deficient in mdr1a expression develop spontaneous colitis. Previous studies using adult bone marrow chimeras indicated that colitis development in this animal model was contingent on P-gp deficiency in radiation-resistant epithelial cells; however, the use of adult animals may mask the role of hematopoietic immune cells in colitis initiation, due to preexisting epithelial abnormalities.

Subjects and Methods: To assess the importance of P-gp expression in intestinal epithelial and hematopoietic-derived cells on colitis induction in FVB.mdr1a−/− animals, we developed a neonatal model of bone marrow reconstitution. FVB/N and FVB.mdr1a−/− adult and neonatal animals were lethally irradiated and reconstituted with bone marrow from FVB/N or FVB.mdr1a−/− donors. Animals were observed for 20 weeks.

Results: Adult FVB/N animals deficient in P-gp expression in hematopoietically derived immune cells developed colitis similar to adult animals deficient in P-gp expression in radiation-resistant epithelial/stromal cells. Neonatal animals deficient in P-gp expression in hematopoietically derived immune cells developed a more histologically significant colitis than those deficient in P-gp expression in epithelial tissue.

Conclusions: The use of a neonatal model of bone marrow reconstitution has revealed a critical role for P-gp expression in hematopoietically derived immune cells in colitis development in the FVB.mdr1a−/− model.

Copyright 2011 by ESPGHAN and NASPGHAN

Login

Article Tools

Share

Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.

Connect With Us

 

 

Twitter

twitter.com/JPGNonline