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

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.