You are here:
PARTICULATE MATTER (PM) INHIBITS NEUROTROPHIN RELEASE FROM A549 CELLS
Farraj, A., Y. Chung, N. H. HaykalCoates, MDW Ward, AND S H. Gavett. PARTICULATE MATTER (PM) INHIBITS NEUROTROPHIN RELEASE FROM A549 CELLS. Presented at American Thoracic Society, San Diego, CA, May 20-25, 2005.
Several investigations have linked PM exposure to the exacerbation of allergic lung diseases. Many PM effects are mediated by cells within the lung including the airway epithelium, eosinophils, and lymphocytes. These cells also produce neurotophins such as NGF and/or express neurotrophin receptors. Neurotrophins are up-regulated in the lungs of asthmatics. In a previous study, we determined that PM-induced exacerbation of allergic airway disease in mice was in part dependent on neurotrophin function. The effect of PM on neurotrophin release from lung epithelium, however, is unclear. We tested the hypothesis that in vitro PM exposure enhances neurotrophin release by A549 cells, a human lung carcinoma cell line that resembles type II cells. Serum starved A549 cells were treated with 1, 10, or 100 ?g/ml of diesel exhaust particles (DEP), residual oil fly ash (ROFA), or Mount St. Helen's dust (MSH) suspended in medium in the presence or absence of IL-1?, a stimulator of NGF release, for 6, 24 or 48 hours. Supernatants were assessed for NGF, neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) via ELISA. IL-1? increased basal secretion of NGF with peak secretion occurring at 24 hr. Basal BDNF secretion peaked at 48 hr. DEP attenuated the release of NGF at 6 and 24 hr, but not 48 hr. ROFA decreased the release of NGF at 6 hr, but not 24 or 48 hr. DEP and ROFA caused a dose-dependent decrease in the secretion of BDNF at 6, 24, and 48 hr. In contrast, MSH had no effect on NGF or BDNF secretion. NT-3 secretion from A549 cells was not detected. The data suggest that PM exposure may result in decreased secretion of neurotrophins from lung epithelium (Supported by NCSU/USEPA CT829470. 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