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DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES TO PENICILLIUM CHRYSOGENUM
Citation:
Chung, Y., N HaykalCoates, M. E. Viana, L B. Copeland, MJK Selgrade, AND MDW Ward. DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES TO PENICILLIUM CHRYSOGENUM. Presented at Asthma Workshop, Research Triangle Park, NC, October 18-19, 2004.
Description:
ABSTRACT
Indoor mold has been associated with development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and its viable conidia can induce allergic responses in a mouse model of allergic penicilliosis. The hypothesis of this study is that soluble components of P. chrysogenum (PCE) can dose-dependently induce cellular, immunologic, and respiratory responses typical of allergic asthma in Balb/c mice. Mice were exposed to 10, 20, 50, or 70 :g of PCE by involuntary aspiration 4 times over a 4 week period. Serum and bronchoalveolar lavage fluid (BALF) were collected immediately prior to the final exposure (Day 0), and at Day 1 and 3 following the final exposure. Lungs were examined histopathologically and scored by degree of inflammatory, degenerative and proliferative changes. Allergen-triggered immediate respiratory responses as well as non-specific airway hyperresponsiveness to methacholine were assessed using barometric whole-body plethysmography. PCE-exposed mice demonstrated dose-dependent increases in: 1) pulmonary edema and cellular damage, 2) BALF total cell numbers including eosinophils, 3) total and specific IgE levels in serum and BALF, and 4) BALF IL-5 levels. Mice with a single exposure to PCE did not exhibit immunologic responses but showed edema and cellular damage at the highest dose (70 :g) of PCE. Mice exposed four times to Metarhizium anisopliae crude antigen (10 :g, as a positive control) showed equivalent or greater allergic asthma-like responses compared to mice exposed four times to 50 or 70 :g of PCE. Histopathologic scores of the lungs demonstrated a dose-dependent increase in severity of lesions due to PCE exposure. Multiple exposures to 70 :g of PCE increased immediate responses as well as airway hyper-responsiveness to methacholine. Taken together, repeated pulmonary challenge with soluble components of P. chrysogenum induced dose-dependent allergic asthma-like responses in mice.