Neurotrophin mediation of allergic airways responses to inhaled diesel particles in mice.

Abstract

Neurotrophins, including nerve growth factor (NGF), partially mediate many features of allergic airways disease including airway hyperresponsiveness. Diesel exhaust particulates (DEP) associated with the combustion of diesel fuel exacerbate many of these allergic airways responses in humans. We tested the hypothesis that DEP-induced enhancement of allergic airways disease in a murine model is dependent on normal function of the low affinity pan-neurotrophin receptor p75(NTR), or tyrosine kinase A (trkA), the primary receptor for NGF. Ovalbumin (OVA)-sensitized and nonallergic BALB/c mice were intranasally instilled with anti-p75(NTR), anti-trkA, or vehicle, 1 h before OVA aerosol challenge, and then exposed nose-only to the particulate matter fraction that was less than 2.5 microns in aerodynamic diameter fraction of Standard Reference Material 2975 DEP (2.0 mg/m(3)) or filtered air for 5 h. One day later, DEP-exposed OVA-allergic mice had significantly greater increases in ventilatory responses to methacholine (Mch), but not increased lung resistance, suggesting that the airflow changes may have originated in the nasal passages. DEP-exposed OVA-allergic mice also had increased lung IL-4 levels relative to all other groups. The instillation of anti-p75(NTR) or anti-trkA completely reversed the DEP-induced increases in ventilatory responses and lung IL-4 protein to levels similar to control mice. OVA-allergic DEP-exposed mice treated with anti-p75(NTR) had significantly less lung resistance in response to Mch relative to OVA-allergic DEP-exposed mice treated with anti-trkA. The results of this study demonstrate that the enhancement of allergic airways responses by DEP exposure is partly dependent on neurotrophins in mice. In addition, neurotrophins that bind p75(NTR), but not trkA, may mediate pulmonary central airways and tissue resistance responses to allergen and DEP exposure.

• Authors: Aimen K Farraj, Najwa Haykal-Coates, Allen D Ledbetter, Paul A Evansky, Stephen H Gavett
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 94 Issue 1 Pg. 183-92 (Nov 2006) ISSN: 1096-6080 [Print] United States
• PMID: 16929010 (Publication Type: Journal Article)

Chemical References

• Nerve Growth Factors
• Receptor, Nerve Growth Factor
• Vehicle Emissions
• Methacholine Chloride
• Interleukin-4
• Immunoglobulin E
• Ovalbumin
• Receptor, trkA

Topics

• Administration, Intranasal
• Animals
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Immunoglobulin E (blood)
• Injections, Intraperitoneal
• Interleukin-4 (immunology, metabolism)
• Lung (drug effects, immunology, metabolism)
• Male
• Methacholine Chloride (administration & dosage, immunology)
• Mice
• Mice, Inbred BALB C
• Nerve Growth Factors (immunology)
• Ovalbumin (administration & dosage, immunology)
• Particle Size
• Plethysmography, Whole Body (methods)
• Receptor, Nerve Growth Factor (antagonists & inhibitors, immunology)
• Receptor, trkA (antagonists & inhibitors, immunology)
• Respiratory Hypersensitivity (chemically induced, immunology)
• Time Factors
• Vehicle Emissions (toxicity)