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J Allergy Clin Immunol. 1999 Nov;104(5):1024-30.

Diesel exhaust particulate induces airway hyperresponsiveness in a murine model: essential role of GM-CSF.

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1
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.

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.

CONCLUSION:

DEP induces airway hyperresponsiveness by stimulating GM-CSF synthesis.

PMID:
10550748
DOI:
10.1016/s0091-6749(99)70084-9
[Indexed for MEDLINE]

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