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COMPARISON OF OVERALL METABOLISM OF 1,2,3,7,8-PENTACHLORODIBENZO-P-DIOXIN (PECDD) IN CYP1A2(-L-)KNOCKOUT (KO) AND C57BL/6N PARENTAL STRAINS OF MICE
Citation:
Diliberto, J J. AND H. Hakk. COMPARISON OF OVERALL METABOLISM OF 1,2,3,7,8-PENTACHLORODIBENZO-P-DIOXIN (PECDD) IN CYP1A2(-L-)KNOCKOUT (KO) AND C57BL/6N PARENTAL STRAINS OF MICE. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
Assessment of immune responses to Penicillium chrysogenum and characterization of its allergens
Yongjoo Chung1, Michael E Viana2, Lisa B Copeland3, and MaryJane K Selgrade3, Marsha D W Ward3. 1 UNC, SPH, Chapel Hill, NC, 2NCSU, CVM, Raleigh, NC, 3US EPA, ORD, NHEERL, RTP, NC, USA
The prevalence of allergic asthma and allergic disease among children has increased in developed countries including the US. Molds have been associated with allergic disease but have not been studied extensively despite their widespread presence in the indoor environment. Penicillium chrysogenum has been associated with both water damaged buildings and sick building syndrome. Our objectives in this study were to assess immune responses to P. chrysogenum and to identify allergenic (IgE inducing) proteins of the fungus. BALB/c mice were exposed four times over a four-week period by involuntary aspiration (IA) to 1, 10 or 100 mg of P. chrysogenum extract (PCE) or Hank's balanced salt solution as vehicle control. Inflammatory control mice were exposed one time to PCE. Positive control mice were exposed to 10 mg of Metarhizium anisopliae extract (MACA). Serum and bronchoalveolar lavage fluid (BALF) were collected before (D0), at 1 (D1) and 3 (D3) days following the final IA exposure. The BALF levels of total protein, lactate dehydrogenase (LDH), and total and differential cell counts were measured. Furthermore, BALF and serum levels of total IgE were assessed. Only mice exposed to 100 g of PCE showed responses different from vehicle control, but some of these mice were moribund. The mice exposed to PCE (100 g) demonstrated significant increases in BALF levels of total protein, LDH, total cell, macrophages, neutrophils, lymphocytes, and eosinophils at D0, D1 and D3, compared to vehicle control. However, mice exposed once to 100 g of PCE (inflammatory control) showed significantly increased levels of total protein, LDH and neutrophils in BALF at D1 and D3. Four exposures to PCE (100 g) also resulted in significantly increased IgE in both serum and BALF compared to vehicle and inflammatory control. Eosinophils in BALF of mice exposed 4x to 100 g of PCE was lower than that of mice exposed to 10 g of MACA but higher than the vehicle or inflammatory control. Western blot analysis using hyperimmune sera against PCE showed 8 IgE inducing proteins in PCE, ranging from approximately 28 to 65.5 kD. Current data indicate that although PCE may induce allergic responses with less potency than MACA, it does contain IgE-inducing proteins. (Supported by UNC/EPA Cooperative Training Agreement CT829471.) (This abstract does not reflect EPA policy.)