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DIFFERENTIAL ALLERGIC AND NEUROTROPHIN RESPONSES TO FUNGAL COMPONENT EXTRACTS IN BALB/C MICE
Citation:
WARD, M. D., N. HAYKAL-COATES, Y. CHUNG, L. B. COPELAND, AND M. K. SELGRADE. DIFFERENTIAL ALLERGIC AND NEUROTROPHIN RESPONSES TO FUNGAL COMPONENT EXTRACTS IN BALB/C MICE. Presented at Society of Toxicology Annual Meeting, New Orleans, LA, March 06 - 10, 2005.
Description:
Metarhizium anisopliae mycelium (MYC), conidia (CON) and inducible protease (IND) extracts were combined to produce the antigen MACA to screen for allergenic potential. Involuntary aspiration (IA) exposure to MACA in BALB/c mice has caused immune, inflammatory and physiological responses characteristic of allergic lung disease. Our objective here was to determine if the component extracts have similar allergenic potential. BALB/c mice received 4 IA of 10 �g of MACA, CON, MYC, IND, or BSA (negative control) in 50 �l HBSS, or HBSS alone (vehicle control) over a 4-week period. Additional mice received 1 exposure to agents as non-allergic controls. Serum and bronchoalveolar lavage fluid (BALF) were collected 3 days (D3) after the final exposure. Mice were assessed for immediate responses following IA exposure and airway hyperresponsiveness to methacholine (MCH; D1 & D3) by whole-body plethysmography, an index of pulmonary resistance and bronchoconstriction (PenH). All fungal extract exposures resulted in elevated BALF total protein, LDH, total cell counts, total IgE and IgA and serum IgE compared to HBSS and BSA controls. These responses were highest in MYC exposed mice, but their PenH was significantly lower compared to the other fungal treatments. To investigate this dichotomy, the level of BALF neurotrophins (NGF, NT-3, NT-4) that have been associated with allergic lung disease were evaluated. All extract exposures resulted in increased levels of the neurotrophins compared to controls. The IND treated mice had the lowest levels of the neurotrophins and significantly higher PenH compared to the other fungal treatments. The rank order of airway responses to the fungal extracts was the inverse of the other endpoints. These data show differences in the magnitude of responses by the M. anisopliae extracts. Additionally, the data suggest that the neurotrophins are not the sole source of the airway responses induced by these extracts. (Supported by UNC/EPA Agreement CT826513. This abstract does not reflect EPA policy.)