Airway mast cells in a rhesus model of childhood allergic airways disease

Laura S. van Winkle, Gregory L. Baker, Jackie K W Chan, Edward S Schelegle, Charles Plopper

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Asthma is a leading cause of morbidity in children. Risk factors include chronic exposure to allergens and air pollution. While chronically activated mast cells contribute to the pathophysiology of asthma in part through their proteases such as chymase and tryptase, previous studies of airway mast cell abundance and distribution in asthmatics have been inconsistent. To determine whether repeated episodic exposures to environmental pollutants during postnatal lung development alter airway mast cell abundance and distribution, we exposed infant rhesus monkeys to a known human allergen, house dust mite antigen (HDMA), and/or a known environmental pollutant, ozone (O3), and quantitatively compared the abundance of tryptase- or chymase-positive mast cells in three airway levels. Mast cells are resident in multiple compartments of the airway wall in infant rhesus monkeys raised from birth in filtered air. Tryptase- and chymase-positive cells were most abundant in trachea and least in terminal bronchioles. The majority of tryptase-positive and almost all chymase-positive cells were in extracellular matrix and smooth muscle bundles. Chronic exposure to HDMA elevated the abundance of both tryptase- and chymase-positive cells in the trachea and intrapulmonary bronchi. Neither exposure to O3 nor HDMA 1 O3 increased mast cell accumulations in the airway wall. We conclude that during postnatal airway development (1) mast cells are a resident airway cell population even in the absence of toxic air contaminants; (2) aeroallergen exposure alters large airway mast cell distribution and abundance, increasing chymase-positive mast cells; and (3) this response is attenuated by exposure to oxidant air pollutants.

Original languageEnglish (US)
Pages (from-to)313-322
Number of pages10
JournalToxicological Sciences
Volume116
Issue number1
DOIs
StatePublished - Apr 19 2010

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Keywords

  • Childhood asthma
  • HDMA
  • Lung development
  • Mast cells
  • Ozone

ASJC Scopus subject areas

  • Toxicology

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