The working hypothesis is that in situations of altered intestinal permeability, which would include hemorrhagic shock and ischemia-reperfusion injury, there is an increased exposure of the lateral surface of the enterocyte. This in turn leads to paracellular adherence (via adhesion molecules) and invasion of normally non-invasive enteric flora. Her design model incorporates an organized and logical approach that utilizes in vitro techniques of cell cultures (Caco-2 and HT-29 cells) and then applies the results in an in vivo model, the mouse. Initially the applicant will attempt to clarify the relationship between enterocyte adhesion molecules (E-AM), bacterial adherence, internalization and intracellular survival, and then investigate the effects of an iatrogenically altered epithelial permeability on E-AM expression and bacteria-enterocyte interactions. Finally she will attempt to clarify the association between E-AM, epithelial permeability, PMN transmigration and bacteria-enterocyte interaction. Adhesion molecules (AM) are felt to play a major role in bacteria-enterocyte interaction. Three families of AM are specifically interesting in this regard: ICAM-1 (modulates PMN migration and decreases epithelial barrier function), E-cadherin (calcium dependent and essential in cell-cell adhesion), and integrins (are located on basolateral surfaces and trigger internalization). Dr. Wells will show the binding pattern, spatial relationship, and effect of monoclonal Ab (mAb) to AM on adherence and internalization in the cultured cells and in the in vivo model. Next she will then investigate the effects of an altered epithelial membrane on these binding patterns using double fluorochrome labeling, also using both the culture line and mouse model. Finally the association between the enterocyte AM, bacteria, and the migrating PMN will be investigated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023484-13
Application #
2671860
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1986-04-01
Project End
2001-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pathology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455