Contribution of allergen-specific and nonspecific nasal responses to early-phase and late-phase nasal responses

• Published in: Journal of allergy and clinical immunology 2008-03, Vol.121 (3), p.718-724
• Main Authors: Miyahara, Satoko, MD, PhD, Miyahara, Nobuaki, MD, PhD, Lucas, Joseph J., PhD, Joetham, Anthony, BS, Matsubara, Shikegi, PhD, Ohnishi, Hiroshi, MD, PhD, Dakhama, Azzeddine, PhD, Gelfand, Erwin W., MD
• Format: Article
• Language: English
• Subjects: Allergens - immunology; Allergic rhinitis; Allergies; Allergy and Immunology; Ambrosia - immunology; Animals; Biological and medical sciences; early-phase; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hypersensitivity - immunology; Immunoglobulin E - blood; late-phase; mast cell; Medical research; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; mouse; Nasal Provocation Tests; Nose; Ovalbumin - immunology; Rhinitis - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Time
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.11.002

Background The relative contributions of the allergen-specific early-phase nasal response and nonspecific nasal response and mast cells to the pathophysiology of allergic rhinitis are not well defined. Objectives To determine the contributions of specific reactivity, nonspecific reactivity, and mast cells to the development of early-phase and late-phase responses using a mouse model of allergic rhinitis. Methods Sensitized wild-type and FcεRI-deficient (FcεRI–/– ) mice were exposed to allergen for 3, 5, or 12 days. As indicators of nasal reactivity, respiratory frequency and nasal resistance were monitored. Results Sensitized mice exposed to 3 days of nasal allergen challenge showed a nonspecific early-phase response. As the number of allergen exposures increased, there was progressive diminution in nonspecific responses with increased allergen-specific early-phase responses and a late-phase response. Sensitized FcεRI–/– mice did not develop nonspecific nasal responses or late-phase responses, but transfer of in vitro –differentiated wild-type mast cells into FcεRI–/– mice restored nonspecific early-phase nasal responses but not the late-phase response. Conclusion These data identify the nonspecific nasal response as a major contributor to the early-phase response, especially during initial allergen exposure, and is dependent on mast cells. Increasing allergen exposure results in increasing allergen-specific responses, converting the nonspecific early-phase response to a late-phase response that is allergen-specific and mast cell–independent.