The purpose of this study was to explore whether repeated exposure to aerosolized ovalbumin (OVA) in the context of local expression of GM-CSF can initiate a Th2-driven, eosinophilic inflammation in the airways. On day -1, Balb/c mice were infected intranasally with an adenovirus construct expressing GM-CSF (Ad/GM-CSF). From day 0 to day 9 mice were exposed daily to an OVA aerosol. Mice exposed to OVA alone did not show any evidence of airway inflammation. Mice receiving both Ad/GM-CSF and aerosolized OVA exhibited marked airway inflammation characterized by eosinophilia and goblet cell hyperplasia. Migration of eosinophils into the airway was preceded by a rise in IL-5 and IL-4. Both IL-5 and class II MHC were critically required to generate airway eosinophilia. After resolution, airway eosinophilia was reconstituted after a single OVA exposure. Flow cytometric analysis of dispersed lung cells revealed an increase in macrophages and dendritic cells expressing B7.1 and B7.2, and expansion of activated (CD69-expressing) CD4 and CD8 T cells in mice exposed to OVA and Ad/GM-CSF. Our data indicate that expression of GM-CSF in the airway compartment increases local antigen presentation capacity, and concomitantly facilitates the development of an antigen-specific, eosinophilic inflammatory response to an otherwise innocuous antigen.
M R Stämpfli, R E Wiley, G S Neigh, B U Gajewska, X F Lei, D P Snider, Z Xing, M Jordana
Title and authors | Publication | Year |
---|---|---|
Differential effects of dendritic cell transfer on airway hyperresponsiveness and inflammation
T Koya, H Matsuda, S Matsubara, N Miyahara, A Dakhama, K Takeda, EW Gelfand |
American journal of respiratory cell and molecular biology | 2009 |
Dendritic Cells
G Lombardi, Y Riffo-Vasquez |
Dendritic Cells | 2009 |
Dendritic Cells
G Lombardi, Y Riffo-Vasquez |
Dendritic Cells | 2009 |
Dendritic Cells
G Lombardi, Y Riffo-Vasquez |
Dendritic Cells | 2009 |
House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells
H Hammad, M Chieppa, F Perros, MA Willart, RN Germain, BN Lambrecht |
Nature Medicine | 2009 |
Concomitant Inhalation of Cigarette Smoke and Aerosolized Protein Activates Airway Dendritic Cells and Induces Allergic Airway Inflammation in a TLR-Independent Way
LJ Robays, EA Lanckacker, KB Moerloose, T Maes, KR Bracke, GG Brusselle, GF Joos, KY Vermaelen |
Journal of immunology (Baltimore, Md. : 1950) | 2009 |
Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke
S Halappanavar, M Russell, MR Stampfli, A Williams, CL Yauk |
BMC Medical Genomics | 2009 |
Between a cough and a wheeze: dendritic cells at the nexus of tobacco smoke-induced allergic airway sensitization
LJ Robays, T Maes, GF Joos, KY Vermaelen |
Mucosal Immunology | 2009 |
Dendritic Cells
S Pai, R Thomas |
Rheumatoid Arthritis | 2009 |
Asthma and COPD
SA Shore, SD Shapiro |
Asthma and COPD | 2009 |
Growth Factors
M Kolb, Z Xing, K Ask, J Gauldie |
Asthma and COPD | 2009 |
Allergy Frontiers: Epigenetics, Allergens and Risk Factors
R Pawankar, ST Holgate, LJ Rosenwasser |
2009 |