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 FcɛRI-deficient (FcɛRI^–/–) 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 FcɛRI^–/– mice did not develop nonspecific nasal responses or late-phase responses, but transfer of in vitro–differentiated wild-type mast cells into FcɛRI^–/– 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.

Key words: Allergic rhinitis, early-phase, late-phase, mouse, mast cell

Abbreviations used: AgEPR, Allergen-specific early-phase nasal response, AR, Allergic rhinitis, BMMC, Bone marrow–derived mast cell, EPR, Early-phase response, LPR, Late-phase response, MC, Mast cell, NNR, Nonspecific nasal response, OVA, Ovalbumin, RF, Respiratory frequency, R_NA, Nasal resistance, RW, Ragweed, WT, Wild-type