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Published ahead of print on November 3, 2003, doi:10.1164/rccm.200308-1094OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 3, February 2004, 378-385

A more recent version of this article appeared on February 1, 2004
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Submitted on August 23, 2003
Accepted on October 30, 2003

Continuous Exposure to House Dust Mite Elicits Chronic Airway Inflammation and Structural Remodeling

Jill R Johnson1, Ryan E Wiley1, Ramzi Fattouh1, Filip K Swirski1, Beata U Gajewska1, Anthony J Coyle2, Jose-Carlos Gutierrez-Ramos2, Russ Ellis3, Mark D Inman3, and Manel Jordana1*

1 Pathology and Molecular Medicine and Division of Respiratory Diseases and Allergy, McMaster University, Hamilton, Ontario, Canada, 2 Millennium Pharmaceuticals Inc., Cambridge, MA, USA, 3 Medicine, Firestone Institute for Resiratory Health, Hamilton, Ontario, Canada

* To whom correspondence should be addressed. E-mail: jordanam{at}mcmaster.ca.

It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin (OVA) intranasally for five consecutive days, followed by two days rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike OVA, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocyte population in the lung with elevated expression of ICOS, a marker of T cell activation and T1/ST2, a marker of Th2 effector cells. We also detected increased and sustained production of Th2-associated cytokines by splenocytes of HDM-exposed mice upon in vitro HDM recall. Histological analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition and peribronchial accumulation of contractile tissue. Additionally, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that while airway inflammation resolved fully, the remodeling changes did not resolve at all and airway hyperreactivity resolved only partly.
Key words: allergy and immunology, asthma, animal, models




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