You are here:
BLOCKADE OF TRKA OR P75 NEUROTROPHIN RECEPTORS ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAYS RESPONSES IN BALB/C MICE
FARRAJ, A., N. HAYKAL-COATES, A. D. LEDBETTER, P. A. EVANSKY, AND S. H. GAVETT. BLOCKADE OF TRKA OR P75 NEUROTROPHIN RECEPTORS ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAYS RESPONSES IN BALB/C MICE. Presented at American Thoracic Society Annual Meeting, San Diego, CA, May 19 - 24, 2006.
Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway resistance. Exposure to diesel exhaust particles (DEP) associated with the combustion of diesel fuel exacerbates allergic airways responses. We tested the hypothesis that DEP-induced enhancement of the hallmark features of allergic airways disease in a murine model is dependent on normal function of either the low affinity pan-neurotrophin receptor p75 or trkA, the primary receptor for NGF. Nonallergic (NA) and ovalbumin (OVA)-allergic BALB/C mice were intranasally instilled with anti-p75, anti-trkA, or vehicle, 1 hour before OVA aerosol challenge. One hour after OVA challenge, the mice were exposed nose-only to the PM2.5 fraction of NIST SRM2975 DEP (2.0 mg/m3) or filtered air for 5 hours. One day later, DEP-exposed OVA-allergic mice had a significantly greater degree of methacholine-induced airflow obstruction and IL-4 levels in lung lining fluid than all other groups. Instillation of anti-p75 or anti-trkA significantly attenuated the DEP-induced increase in airflow obstruction to levels similar to NA mice. Anti-p75 or anti-trkA also attenuated the DEP-induced increase in lung IL-4 levels. The data demonstrate that neurotrophins play a role in DEP-induced exacerbation of allergic airways responses (This abstract does not reflect EPA policy; CT829470).
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