The over all hypothesis of this application is that the endothelial cell (by expressing chemokines and adhesion molecules) plays a central role in eosinophil adhesion, activation and recruitment at sites of allergic inflammation. Therefore, the objective of this grant application is to investigate the role of individual adhesion molecules, as well as cytokines, which modulate both adhesion of eosinophils to endothelium and the growth of new blood vessels in vitro and in vivo at sites of allergic inflammation. In vivo studies of endothelium will utilize both neutralizing antibodies, as well as adhesion molecule and cytokine knockout mice, to assess the relative importance of an individual adhesion molecule or cytokine to allergen mediated angiogenesis, adhesion (fucosyl transferase VII knockout mice whose eosinophils do not express the adhesion molecule sLex), and transmigration of eosinophils (eotaxin knockout mice) across endothelium. The in vitro studies of eosinophil adhesion to endothelium will use intravital microscopy and a flow chamber to determine the role of an LDV motif contained in the alpha 4 chain of VLA-4 in mediating eosinophil rolling on endothelial adherent eosinophils.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI033977-06
Application #
6137179
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Plaut, Marshall
Project Start
1994-05-01
Project End
2002-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
6
Fiscal Year
2000
Total Cost
$266,606
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Zhang, Mai; Angata, Takashi; Cho, Jae Youn et al. (2007) Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils. Blood 109:4280-7
Lim, Dae Hyun; Cho, Jae Youn; Miller, Marina et al. (2006) Reduced peribronchial fibrosis in allergen-challenged MMP-9-deficient mice. Am J Physiol Lung Cell Mol Physiol 291:L265-71
Broide, David H (2005) DNA vaccines: an evolving approach to the treatment of allergic disorders. Allergy Asthma Proc 26:195-8
Cho, Jae Youn; Miller, Marina; Baek, Kwang Je et al. (2004) Immunostimulatory DNA inhibits transforming growth factor-beta expression and airway remodeling. Am J Respir Cell Mol Biol 30:651-61
Cho, Jae Youn; Miller, Marina; Baek, Kwang Je et al. (2004) Inhibition of airway remodeling in IL-5-deficient mice. J Clin Invest 113:551-60
Youn, Cho Jae; Miller, Marina; Baek, Kwang Je et al. (2004) Immunostimulatory DNA reverses established allergen-induced airway remodeling. J Immunol 173:7556-64
Ikeda, Reid K; Miller, Marina; Nayar, Jyothi et al. (2003) Accumulation of peribronchial mast cells in a mouse model of ovalbumin allergen induced chronic airway inflammation: modulation by immunostimulatory DNA sequences. J Immunol 171:4860-7
Ikeda, Reid K; Nayar, Jyothi; Cho, Jae Youn et al. (2003) Resolution of airway inflammation following ovalbumin inhalation: comparison of ISS DNA and corticosteroids. Am J Respir Cell Mol Biol 28:655-63
Broide, David H; Miller, Marina; Castaneda, Diego et al. (2002) Core 2 oligosaccharides mediate eosinophil and neutrophil peritoneal but not lung recruitment. Am J Physiol Lung Cell Mol Physiol 282:L259-66
Miller, Marina; Cho, Jae Youn; Baek, Kwang Je et al. (2002) Plasmid DNA encoding the respiratory syncytial virus G protein protects against RSV-induced airway hyperresponsiveness. Vaccine 20:3023-33

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