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House Dust Mite Facilitates Ovalbumin-specific Allergic Sensitization and Airway Inflammation

Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics, and Department of Pathology and Molecular Medicine, and Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada

Correspondence and requests for reprints should be addressed to Manel Jordana, M.D., PhD., Department of Pathology and Molecular Medicine, MDCL 4013, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5 Canada. E-mail: jordanam{at}mcmaster.ca

Rationale: Mouse models of allergic airway disease have greatly contributed to our understanding of disease induction and pathogenesis. Although these models typically investigate responses to a single antigen or allergen, humans are frequently exposed to a myriad of allergens, each with distinct antigenic potential. Objectives: Given that airway exposure to ovalbumin (OVA), a prototypic innocuous antigen, induces inhalation tolerance, we wished to investigate how this response would be altered if OVA were encountered concurrently with a house dust mite extract (HDM), which we have recently shown is capable of eliciting a robust allergic airway inflammatory response that is mediated, at least in part, by granulocyte-macrophage colony–stimulating factor. Methods: Balb/c mice were exposed daily to HDM (intranasally) followed immediately by exposure to aerosolized OVA for 5 weeks. To allow the inflammatory response elicited by HDM to subside fully, mice were then allowed to rest, unexposed, for 8 weeks, at which time they were rechallenged with aerosolized OVA for 3 consecutive days. Measurements and Main Results: At this time, we observed a robust eosinophilic inflammatory response in the lung that was associated with an increase in bronchial hyperreactivity. Moreover, we documented significantly elevated serum levels of OVA-specific IgE and IgG₁ and increased production of the Th2 cytokines interleukin 4 (IL-4), IL-5, and IL-13 by splenocytes stimulated in vitro with OVA. Conclusion: Our data demonstrate the potential of a potent allergen such as HDM to establish a lung microenvironment that fosters the development of allergic sensitization to otherwise weak or innocuous antigens, such as OVA.

Key Words: allergic sensitization • allergy inflammation • lung • mouse

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