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DIESEL PARTICLE INSTILLATION ENHANCES INFLAMMATORY AND NEUROTROPHIN RESPONSES IN THE LUNGS OF ALLERGIC BALB/C MICE
FARRAJ, A., N. HAYKAL-COATES, B. SUTHERLAND, AND S. H. GAVETT. DIESEL PARTICLE INSTILLATION ENHANCES INFLAMMATORY AND NEUROTROPHIN RESPONSES IN THE LUNGS OF ALLERGIC BALB/C MICE . Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airways resistance and inflammation. Antibody blockade of NGF attenuates airways resistance associated with the allergen-specific airways responses in mice. Exposure to diesel exhaust particles (DEP) associated with the combustion of diesel fuel exacerbates allergic airways responses. We tested the hypothesis that the intranasal instillation of DEP in allergic mice will increase the hallmark features of allergic airways disease including increased neurotrophin production. Ovalbumin (OVA)-sensitized and non-sensitized BALB/C mice were intranasally instilled six times over two weeks with 10 (DEP1) or 50 (DEP2) ¿g of the PM2.5 fraction of NIST SRM-2975 DEP or saline alone. The mice were then challenged with an OVA aerosol. Non-allergic mice instilled with DEP1 had a 2.7-fold increase in macrophages in the lung lining fluid one day after challenge, while those instilled with DEP2 had a 3-fold increase in macrophages and a 19-fold increase in eosinophils relative to saline instilled mice. OVA-allergic mice instilled with saline had increases in macrophages (2-fold) and eosinophils (7.1-fold) relative to non-allergic mice. DEP1 did not enhance OVA-induced responses. DEP2-exposed OVA-allergic mice had increases in macrophages (1.61-fold), eosinophils (1.45-fold), and neutrophils (1.78-fold) in the lung lining fluid one day after challenge relative to saline-instilled mice. DEP2 instillation also increased levels of the neurotrophin NT-3 (2-fold) in the lung lining fluid and serum IgE (1.4-fold) relative to saline-instilled mice. Three days after OVA challenge, DEP2-exposed OVA-allergic mice had increased macrophages (1.4-fold), eosinophils (4.4-fold) and neutrophils (1.53-fold) in the lung lining fluid but no change in NT-3 or IgE levels relative to saline-instilled mice. Neurotrophin upregulation may trigger DEP-induced enhancement in serum IgE and pulmonary inflammation in allergic mice (This abstract does not reflect EPA policy).
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
EXPERIMENTAL TOXICOLOGY DIVISION
PULMONARY TOXICOLOGY BRANCH