You are here:
BLOCKADE OF NERVE GROWTH FACTOR (NGF) RECEPTOR TRKA ATTENUATES DIESEL EXHAUST PARTICULATE MATTER (DEP) ENHANCEMENT OF ALLERGIC INFLAMMATION
Citation:
Farraj, A., N. H. HaykalCoates, A. D. Ledbetter, P A. Evansky, AND S H. Gavett. BLOCKADE OF NERVE GROWTH FACTOR (NGF) RECEPTOR TRKA ATTENUATES DIESEL EXHAUST PARTICULATE MATTER (DEP) ENHANCEMENT OF ALLERGIC INFLAMMATION. Presented at American Thoracic Society, San Diego, CA, May 20-25, 2005.
Description:
Recent studies have shown that asthmatics have increased levels of the neurotrophin, NGF, in their lungs. In addition, antibody blockade of NGF in mice attenuates airway resistance associated with allergic airway responses. DEP has been linked to asthma exacerbation in many cities with vehicular traffic congestion. Cell types affected by DEP, including eosinophils, macrophages, lymphocytes and the airway epithelium, also produce NGF and/or express the TrkA receptor, the primary receptor for NGF in the lung. The relationship between DEP exposure and neurotrophins, however, is unclear. We tested the hypothesis that DEP-induced enhancement of the hallmark features of allergic airway disease in a murine model is dependent on TrkA function. Nonallergic (NA) and ovalbumin (OVA)-allergic C57BL/6J mice were intranasally instilled with an antibody against the TrkA receptor or saline alone 1 hour before OVA challenge. The mice were then exposed nose-only to the PM2.5 fraction of SRM2975 DEP (0.85 mg/m3) or air alone for five hours, beginning 1 hour after OVA challenge (n=9/group). Two days later, DEP exposed OVA-allergic mice developed increased levels of bronchoalveolar lavage fluid eosinophils, neutrophils and lymphocytes relative to air exposed OVA-allergic mice. Instillation of anti-TrkA significantly reduced the total number of eosinophils, neutrophils, and lymphocytes relative to the DEP exposed OVA-allergic mice instilled with saline alone. The data demonstrate that neurotrophins may play a role in DEP exacerbation of allergic responses (Supported by NCSU/USEPA CT829470. This abstract does not reflect EPA policy).