Lung disease as a consequence of bacterial infection in many situations is marked by severe inflammation, particularly the accumulation of large numbers of neutrophils in the luminal space along the respiratory tract. It is currently unclear what bacterial factors can trigger this response and exactly how the neutrophils are directed to the site of infection. In the preliminary data of this proposal we have developed an in vitro model for airway inflammation using polarized alveolar epithelial monolayers and neutrophils. We have shown that a variety of bacteria are capable of inducing neutrophil transmigration across the alveolar epithelial monolayers. This phenomenon does not appear to be mediated by LPS and the mechanism of induction of neutrophil transmigration is independent of IL-8 secretion, It is the intention of this proposal to identify the bacterial factors responsible for promoting the neutrophil migration as well as to further define the role of the epithelial monolayer in this process. Results obtained from the following proposal may shed light on diseases involving bacterial mediated lung inflammation such as cystic fibrosis and should also provide new strategies directed towards treating lung disease. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI054054-02
Application #
6819993
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Prograis, Lawrence J
Project Start
2003-07-01
Project End
2005-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$47,296
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Hurley, Bryan P; McCormick, Beth A (2004) Intestinal epithelial defense systems protect against bacterial threats. Curr Gastroenterol Rep 6:355-61
Croker, B P; Gilkeson, G; Morel, L (2003) Genetic interactions between susceptibility loci reveal epistatic pathogenic networks in murine lupus. Genes Immun 4:575-85