Published ahead of print on May 5, 2005, doi:10.1164/rccm.200502-198OC Am. J. Respir. Crit. Care Med., Volume 172, Number 3, August 2005, 314-321 A more recent version of this article appeared on August 1, 2005
Submitted on February 8, 2005 House Dust Mite Facilitates Ovalbumin-specific Allergic Sensitization and Airways InflammationRamzi Fattouh1,1 Division of Respiratory Diseases and Allergy, Department of Pathology and Molecular Medicine, McMaster University, Centre for Gene Therapeutics, Hamilton, Ontario, Canada, 2 Department of Medicine, McMaster University, Firestone Institute for Respiratory Health, Hamilton, Ontario, Canada * To whom correspondence should be addressed. E-mail: jordanam{at}mcmaster.ca.
Rationale: Mouse models of allergic airway disease have greatly contributed to our understanding of disease induction and pathogenesis. While 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 OVA, a prototypical 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 after 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 IL-4, -5, and -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: Allergy, Lung, Allergic sensitization, Mouse, Inflammation
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