Original contribution
Biological effects of diesel exhaust particles (DEP). III. Pathogenesis of asthma like symptoms in mice

https://doi.org/10.1016/0891-5849(96)00032-9Get rights and content

Abstract

Chronic airway inflammation, mucus hypersecretion, reversible airway constriction, and bronchial hyperresponsiveness are important pathogenic features of asthma. We found that diesel exhaust particles (DEP) instilled intratracheally and repeatedly to mice (once/week for 16 weeks) caused marked infiltration of inflammatory cells, proliferation of goblet cells, increased mucus secretion, respiratory resistance, and airway constriction. Eosinophils in the submucosa of the proximal bronchi and medium bronchioles increased eightfold following instillation. Eosinophil infiltration was significantly suppressed by pretreatment with polyethyleneglycol-conjugated superoxide dismutase (PEG-SOD). Bound sialic acid concentrations in bronchial alveolar lavage fluids, an index of mucus secretion, increased with DEP, but were suppressed by pretreatment with PEG-SOD. Goblet cell hyperplasia, airway narrowing, and airway constriction also were observed with DEP. Respiratory resistance in the DEP-group to acetylcholine was 11 times higher than in controls, and the increased resistance was significantly suppressed by PEG-SOD pretreatment. These findings suggest that DEP and/or oxygen radicals derived from DEP cause bronchial asthma in mice.

References (82)

  • T. Ichinose et al.

    Biological effects of diesel exhaust particles (DEP). II. Acute toxicity of DEP introduced into lungs by intratracheal instillation

    Toxicology

    (1995)
  • C.J.A. Doelman et al.

    Oxygen radicals in lung pathology

    Free Radic. Biol. Med.

    (1990)
  • F.M. Cuss et al.

    Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man

    Lancet.

    (1986)
  • E. Masini et al.

    Histamine release from rat mast cells induced by metabolic activation of polyunsaturated fatty acids into free radicals

    Biochem. Pharmacol.

    (1990)
  • E.B. Weiss et al.

    Leukotriene-associated oxygen metabolites induces airway hyperreactivity

    Chest

    (1986)
  • E. Frigas et al.

    The eosinophil and pathophysiology of asthma

    J. Allergy. Clin. Immunol.

    (1986)
  • G.J. Gleich

    The eosinophil and bronchial asthma; Current understanding

    J. Allergy Clin. Immunol.

    (1990)
  • P.J. Barnes

    Reactive oxygen species and airway inflammation

    Free Radic. Biol. Med.

    (1990)
  • T.D. Lee et al.

    Increased biosynthesis of platelet-activating factor in activated human eosinophils

    J. Biol. Chem.

    (1984)
  • G.A. Visner et al.

    Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin-1, and tumor necrosis factor

  • M. Ono et al.

    Induction of Mn-superoxide dismutase by tumor necrosis factor, interleukin-I and interleukin-6 in human hepatoma cells

    Biochem. Biophys. Res. Commun.

    (1992)
  • A.Y. Watson et al.

    Air pollution, the automobile and public health

    (1988)
  • V.B. Vouk et al.

    Metallic elements in fossil fuel combustion products: Amounts and from of emissions and evaluation of carcinogenicity and mutagenicity

    Environ. Health Perspect.

    (1983)
  • D. Schuetzle

    Sampling of vehicle emissions for chemical analysis and biological testing

    Environ. Health Perspect.

    (1983)
  • D. Schuetzle et al.

    Factors influencing the emission of vapor and particulate phase components from diesel engines

  • D. Schuetzle et al.

    Bioassay-directed chemical analysis in environmental research

    Anal. Chem.

    (1986)
  • Y.S. Cheng et al.

    Characterization of diesel exhaust in a chronic inhalation study

    Am. Ind. Hyg. Assoc. J.

    (1984)
  • J. Lewtas

    Evaluation of the mutagenicity and carcinogenicity of the morter vehicle emissions in short-term bioassay

    Environ. Health Perspect.

    (1983)
  • U. Rannugg

    Data from short-term tests on motor vehicle exhausts

    Environ. Health Perspect.

    (1983)
  • R.O. McClellan

    Health effects of exposure to diesel exhaust particles

    Annu. Rev. Pharmacol. Toxicol.

    (1987)
  • N. Ishinishi et al.

    Carcinogenic and mutagenic effects of diesel engine exhaust

  • H. White et al.

    A long-term inhalation study evaluates the pulmonary effects of diesel emissions

    J. Appl. Toxicol.

    (1983)
  • U. Heinrich et al.

    Chronic effects on the respiratory tract of hamsters, mice and rats after long-term inhalation emissions

    J. Appl. Toxicol.

    (1986)
  • K. Iwai et al.

    Chronic inhalation studies of diesel exhaust gas-Morphological changes observed in intra-and extra-pulmonary organs

    J. Jpn. Soc. Air Pollut.

    (1986)
  • T. Suzuki et al.

    Long-term inhalation experiments of the health effects of diesel exhaust

  • Y. Kawabata et al.

    Lung injury and carcinogenesis following intratracheal instillation of diesel soot particle to the lung

    J. Jpn. Soc. Air. Pollut.

    (1988)
  • M. Muranaka et al.

    Adjuvant activity of diesel-exhaust particles for the production of IgE antibody in mice

    J. Allergy Clin. Immunol.

    (1986)
  • P.J. Barnes et al.

    Recent advances in asthma

    Postgrad. Med. J.

    (1992)
  • P.G.J. Burney

    Epidemiology

    Br. Med. Bull.

    (1992)
  • T. Haahtela et al.

    Prevalence of asthma in Finnish young men

    Br. Med. J.

    (1990)
  • P.G. Burney et al.

    Has the prevalence of asthma increased in children?

  • Cited by (188)

    • Vesicular acetylcholine transport deficiency potentiates some inflammatory responses induced by diesel exhaust particles

      2019, Ecotoxicology and Environmental Safety
      Citation Excerpt :

      Alterations in the extracellular matrix components (Araujo et al., 2008), airway smooth muscle hypertrophy (James et al., 2012), goblet cell hypertrophy and hyperplasia with increased mucus production are known features of lung remodeling. These alterations are involved in several lung diseases including inflammation induced by air pollution (Ishihara and Kagawa, 2002; Sagai et al., 1996). To determine the effect of DEP instillation in lung remodeling processes we measured collagen and elastic fibers content in lung alveolar septa of VAChT-KD mice and WT controls.

    • Impact of diesel exhaust exposure on the liver of mice fed on omega-3 polyunsaturated fatty acids-deficient diet

      2018, Food and Chemical Toxicology
      Citation Excerpt :

      The particulate phase of diesel exhaust (DE) is thought to contribute to the increased prevalence of acute and chronic airway diseases (de Kok et al., 2006; Li et al., 2003). It is clear that DE causes lung cancer, allergic rhinitis, and bronchial asthma–like diseases (McClellan, 1987; Muranaka et al., 1986; Sagai et al., 1996; Steenland et al., 1998). DE is a complex mixture of gaseous and particulate components.

    View all citing articles on Scopus
    View full text