title: Diesel exhaust particulate induces airway hyperresponsiveness in a murine model: essential role of GM-CSF.
abstract: BACKGROUND
  Inhaled pollutants were recently shown to be responsible for an increased incidence of airway allergic diseases, including asthma. A common feature of all forms of asthma is airway hyperresponsiveness.
  
  
  OBJECTIVE
  Our purpose was to elucidate the effects of diesel exhaust particulate (DEP), one of the most prevalent inhaled pollutants, on airway responsiveness.
  
  
  METHODS
  A/J and C57Bl/6 mice were used; the former are genetically predisposed to be hyperresponsive to acetylcholine, whereas the latter are not. DEP was administered intranasally for 2 weeks, after which pulmonary function was analyzed by whole-body plethysmography.
  
  
  RESULTS
  Intranasal administration of DEP increased airway responsiveness to acetylcholine in both A/J and C57Bl/6 mice and induced displacement of ciliated epithelial cells by mucus-secreting Clara cells. The effect was mediated by M(3) muscarinic receptors. Acetylcholine-evoked bronchial constriction was reversed by administration of terbutaline, a beta(2)-adrenergic antagonist, which is also characteristic of human asthma. Intranasal administration of antibody raised against GM-CSF abolished DEP-evoked increases in airway responsiveness and Clara cell hyperplasia. The antibody raised against IL-4 also inhibited DEP-evoked increases in airway responsiveness. However, it was to a lesser extent compared with antibody against GM-CSF. In addition, DEP stimulated GM-CSF messenger RNA expression in the lung.
  
  
  CONCLUSIONS
  DEP induces airway hyperresponsiveness by stimulating GM-CSF synthesis.
authors.affiliation: Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: N
authors.initials: N
authors.lastname: Yamashita
authors.forename: M
authors.initials: M
authors.lastname: Tajima
authors.forename: T
authors.initials: T
authors.lastname: Miyasaka
authors.forename: J
authors.initials: J
authors.lastname: Nakano
authors.forename: M
authors.initials: M
authors.lastname: Nakajima
authors.forename: A
authors.initials: A
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Horiuchi
authors.forename: K
authors.initials: K
authors.lastname: Mano
authors.forename: T
authors.initials: T
authors.lastname: Miyamoto
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005742:Gasoline / Q000009:adverse effects*; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D001335:Vehicle Emissions / Q000009:adverse effects*
chemical_list: D005742:Gasoline; D015848:Interleukin-5; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D015847:Interleukin-4; D007073:Immunoglobulin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000109:Acetylcholine