Abstract

This proposal addresses two questions about asthma: first, how does the pulmonary eosinophilic inflammatory response differ in ragweed allergic subjects with and without asthma? and second, what elements of the IgE-mediated inflammatory response are associated with the prolonged and ongoing pulmonary eosinophilic inflammation observed in ragweed allergic asthmatics? The hypothesized answer to both is GM-CSF.
The first aim i s to characterize the magnitude, kinetics and relative importance of the increased secretion of GM-CSF over a 16-day period following segmental antigen challenge.
In specific aim 2, the investigators seek to define the cellular sources of the GM-CSF and in aim 3, they propose to determine whether prolonged expression of this cytokine differentiates ragweed allergic asthmatics from allergic rhinitics.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024509-11
Application #
6341566
Study Section
Lung Biology and Pathology Study Section (LBPA)
Program Officer
Banks-Schlegel, Susan P
Project Start
1986-09-15
Project End
2002-12-31
Budget Start
2001-01-01
Budget End
2002-12-31
Support Year
11
Fiscal Year
2001
Total Cost
$274,607
Indirect Cost

  Institution

Name
Thomas Jefferson University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107

  Publications

Hastie, Annette T; Wu, Min; Foster, Gayle C et al. (2006) Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and beta2-agonist use. Respir Res 7:25
Batra, V; Musani, A I; Hastie, A T et al. (2004) Bronchoalveolar lavage fluid concentrations of transforming growth factor (TGF)-beta1, TGF-beta2, interleukin (IL)-4 and IL-13 after segmental allergen challenge and their effects on alpha-smooth muscle actin and collagen III synthesis by primary human lu Clin Exp Allergy 34:437-44
Peters, Stephen P (2003) Heterogeneity in the pathology and treatment of asthma. Am J Med 115 Suppl 3A:49S-54S
Hastie, Annette T; Batra, Vikas; Khurana, Sandhya et al. (2003) Modulation of vasodilator-stimulated phosphoprotein in vivo in human epithelial cells by segmental allergen challenge and beta2-agonist therapy. Chest 123:377S
Batra, Vikas; Khurana, Sandhya; Musani, Ali I et al. (2003) Concentration of cytokines and growth factors in BAL fluid after allergen challenge in asthmatics and their effect on alpha-smooth muscle actin and collagen III synthesis by human lung fibroblasts. Chest 123:398S-9S
Niazi, Sultan; Robertson, Noreen M; Agrawal, Ashish et al. (2003) Overlap between death receptor and non-receptor-mediated mechanisms during apoptosis in human eosinophils. Chest 123:345S
Peters, Stephen P (2003) Leukotriene receptor antagonists in asthma therapy. J Allergy Clin Immunol 111:S62-70
Hastie, Annette T; Kraft, Walter K; Nyce, Kristin B et al. (2002) Asthmatic epithelial cell proliferation and stimulation of collagen production: human asthmatic epithelial cells stimulate collagen type III production by human lung myofibroblasts after segmental allergen challenge. Am J Respir Crit Care Med 165:266-72
Robertson, Noreen M; Zangrilli, James G; Steplewski, Andrzej et al. (2002) Differential expression of TRAIL and TRAIL receptors in allergic asthmatics following segmental antigen challenge: evidence for a role of TRAIL in eosinophil survival. J Immunol 169:5986-96
Loza, Matthew J; Peters, Stephen P; Zangrilli, James G et al. (2002) Distinction between IL-13+ and IFN-gamma+ natural killer cells and regulation of their pool size by IL-4. Eur J Immunol 32:413-23

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