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Augmentation of inflammatory and immune responses to inhaled antigen by combined exposure to beta-nephthoflavone (BNF).
Weissman-DN; Seigel-PD; Zhuang-Z; Lewis-DM
J Allerg Clin Immunol 2001 Feb; 107(2):S146
Combined exposures of the respiratory tract to diesel exhaust particulate (DEP) and allergen are associated with an enhanced allergen-specific IgE response. Polycyclic aromatic hydrocarbons (PAH) are thought to at least partially mediate this effect of DEP. To further evaluate the ability of PAH to modulate responses to inhaled antigen, combined exposures to a representative PAH, BNF, and an inhaled protein antigen, ovalbumin (OVA), were studied in C57BL/6 mice. BNF (100 mg/kg) dissolved in olive oil (OO) or OO alone were administered IP on days 0, 4, and 8. Both groups were also exposed to OVA by aerosol (35 mg/m3, 30 min/day x 9 days). Serum anti-OVA IgG concentrations were not different in the BNF and OO groups at days 0 and 7, but were significantly greater in the BNF group at days 14,17, and 21. To assess whether the BNF-treated mice were at greater risk of pulmonary inflammatory responses on re-exposure to OVA, animals from both groups underwent aerosol challenge between days 28 and 36 (35 mg/m3 x 30 min). Mice were sacrificed and BAL examined 48 hr later. BNF-treated mice had significantly increased BAL total cell, lympocyte, and eosinophil counts relative to OO-treated mice, with increases in BAL lymphocytes being the most marked. Trends were also noted for increased BAL macrophages and PMN. To assess the potential role of the aryl hydroxyl receptor (Ahr) in mediating the effects of BNF, exposure as noted abover were performed using B6 mice congenic for Ahr unresponsiveness due to substitution of the Ahrd locus from DBA mice (B6.D, Ahrd). Although the differences were not as marked as those noted for C57BL/6 mice, Ahrd mice treated with BNF also developed significantly greater serum anti-OVA IgG responses than those treated with 00 after aerosol exposure to OVA. After aerosol challenge with OVA, Ahrd mice treated with BNF had significantly greater BAL total cell, macrophage and lymphocyte counts being the most markedly increased. A trend was also noted for increased BAL eosinophils. These data demonstrate that exposure to at least one representative PAH can increase the level of in vivo inflammatory and immune responses induced by inhaled antigen. Furthermore, augmentation of response can occur even in the presence of a relatively poorly functional Ahr, suggesting an important role for other pathways in mediating PAH effect.
Immune-system; Antigens; Respiratory-system-disorders; Diesel-exhausts; Exposure-levels; Hydrocarbons; Immune-reaction; Exposure-assessment; Allergens; Polycyclic-aromatic-hydrocarbons; Laboratory-animals; Animals; Animal-studies; Lymphocytes; In-vivo-studies; Pulmonary-system-disorders; Particulates; Particulate-dust
Abstract; Conference/Symposia Proceedings
Issue of Publication
Journal of Allergy and Clinical Immunology
Page last reviewed: March 11, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division