Inhalation of diesel exhaust enhances allergen-related eosinophil recruitment and airway hyperresponsiveness in mice

Toxicol Appl Pharmacol. 1998 Jun;150(2):328-37. doi: 10.1006/taap.1998.8437.

Abstract

We have previously shown that intratracheal instillation of suspension of diesel exhaust particles enhances allergen-related eosinophilic airway inflammation, airway hyperresponsiveness, and local expression of interleukin (IL)-5 and granulocyte macrophage-colony stimulating factor (GM-CSF) in mice. The present study was designed to elucidate the effects of daily inhalation of diesel exhaust (DE) on the allergen-related respiratory disease. ICR mice were exposed for 40 weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 with aerosol allergen challenges (1% ovalbumin in isotonic saline for 6 min) at 3-week intervals during the last 24 weeks of exposures. Exposure to DE enhanced allergen-related eosinophil recruitment to the submucosal layers of the airways and to the bronchoalveolar space, and increased protein levels of GM-CSF and IL-5 in the lung in a dose-dependent manner compared to exposure to clean air. There were strong correlations between the number of eosinophils in bronchoalveolar lavage (BAL) fluid and IL-5 concentrations in BAL supernatants and lung tissue supernatants. In addition, the increases in eosinophil recruitment and local cytokine expression were accompanied by goblet cell proliferation in the bronchial epithelium and airway hyperresponsiveness to inhaled acetylcholine. In contrast, the control mice exposed for 40 weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 without allergen provocation showed no eosinophil recruitment to the submucosal layers of the airways nor to the bronchoalveolar space and few goblet cells in the bronchial epithelium. The present study provides experimental evidence that daily inhalation of DE can enhance allergen-related respiratory diseases such as allergic asthma. This effect may be mediated by the enhanced local expression of IL-5 and GM-CSF. Increased ambient levels of DE may be implicated in the increasing prevalence of bronchial asthma in recent years.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Allergens*
  • Animals
  • Asthma / chemically induced
  • Asthma / etiology
  • Bronchial Hyperreactivity / etiology*
  • Bronchial Hyperreactivity / immunology
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Division / drug effects
  • Eosinophils / drug effects*
  • Eosinophils / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
  • Immunoglobulin G / analysis
  • Interleukin-5 / analysis
  • Interleukin-5 / biosynthesis*
  • Leukocyte Count
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Ovalbumin
  • Vehicle Emissions / toxicity*

Substances

  • Allergens
  • Immunoglobulin G
  • Interleukin-5
  • Vehicle Emissions
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Ovalbumin