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DOSE-DEPENDENT INCREASE IN THE PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM-INDUCED ALLERGIC ASTHMA MODEL
Citation:
Chung, Y., A. Farraj, N HaykalCoates, S H. Gavett, AND MDW Ward. DOSE-DEPENDENT INCREASE IN THE PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM-INDUCED ALLERGIC ASTHMA MODEL. Presented at Society of Toxicology Annual Meeting, New Orleans, LA, March 06 - 10, 2005.
Description:
Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthma as well as in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated pulmonary challenge with Penicillium chrysogenum extract (PCE) induced dose-dependent allergic asthma-like responses in mice. The aim of this study was to investigate whether exposures to PCE could increase the production of neurotrophins in bronchoalveolar lavage fluid (BALF) of PCE challenged mice. Mice were exposed to 10, 20, 50, or 70 ?g of PCE by involuntary aspiration four times over one month. BALF was collected before (Day 0), and at Day 1 and 3 following the final exposure. The levels of NGF, NT-3, and NT-4 were determined by ELISA. Lungs collected at Day 0, 1, and 3 were perfusion-fixed and processed for immunohistochemical examination of NGF production. PCE-exposed mice had dose-dependent increases in NGF, NT-3, and NT-4. A single exposure to PCE did not significantly increase the production of the neurotrophins. Four exposures to Metarhizium anisopliae crude antigen (MACA, 10 ?g, a positive control for allergic asthma), however, resulted in the production of neurotrophins that was equal to or greater than that caused by four exposures to 50 or 70 ?g of PCE. Exposures to PCE or MACA caused an increase in positive immunohistochemical staining for NGF in epithelial and smooth muscle cells in addition to infiltrated cells such as monunuclear cells and macrophages. Taken together, mice that received multiple exposure to PCE had dose-dependent increases in NGF, NT-3, and NT-4 in BALF. This is the first study to link fungal allergic asthma in an experimental model with enhanced production of neurotrophins in the airways. (Supported by UNC/EPA Cooperative Training Agreement CT829471 and this abstract does not reflect EPA policy.)