Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inflammation

The aim of this study was to investigate production and cellular sources of brain-derived neurotrophic factor (BDNF) production in allergic asthma. Fo r this purpose a mouse model of chronic and severe ovalbumin (OVA)-induced airway inflammation was developed. Allergen-exposed mice developed elevated immunoglobulin E titers; airway inflammation with influx of lymphocytes, m onocytes, and eosinophils; and airway hyperresponsiveness. In addition to a n influx of inflammatory cells, interleukin (IL)-4 and IL-5 production were enhanced, macrophages showed morphologic signs of activation, and airway e pithelium was thickened and displayed a goblet-cell hyperplasia with a mark ed mucus production. BDNF was detected using in situ hybridization and enzy me-linked immunosorbent assay. Constitutive expression of BDNF messenger RN A (mRNA) was observed in the respiratory epithelium of sensitized and nonse nsitized mouse lungs. In addition, BDNF mRNA was detected in airway inflamm atory infiltrations and bronchoalveolar lavage fluid (BALF) cells of OVA-se nsitized and aerosol-challenged mice. Highest BDNF protein levels were dete cted in BALF after long-term allergen aerosol exposure. Analysis of BDNF pr oduction by isolated lymphocyte subsets revealed T but not B cells as a cel lular source of BDNF. In addition, activated alveolar macrophages were iden tified as BDNF-positive cells. These data indicate that in allergic airway inflammation BDNF production is upregulated and immune cells serve as a sou rce of BDNF.