The goal of this proposal is to study the immunologic response which occurs in vivo after nasal mast cell activation and to relate this response to clinical disease. We will focus on the late phase response using an in vivo model which allows measurement of inflammatory mediators after intranasal challenge with antigen or cold dry air. Recent work has demonstrated the presence of histamine, TAME-esterase activity and kinins during both the early and late nasal response, whereas prostaglandin D2 is only present during the early response. We will explore whether this difference is related to the cell type involved. For example, are mast cells involved in the immediate response and basophils in the late? Initial experiments will determine the pattern of other mediators such as leukotrienes and Charcot Leyden Crystals in both the early and late response. In addition, using microscopy, we will attempt to identify basophils and/or mast cells in nasal secretions following challenge. The late phase response will be related to the clinical disease of allergic rhinitis using two approaches. First, we will evaluate the effect of both topical and systemic steroids, which are clinically effective drugs which have no effect on the early response to nasal challenge. Second, in collaboration with an ongoing immunotherapy project, we will challenge individuals before and after immunotherapy to study whether individuals with a late phase response respond to seasonal exposure differently than those with only an immediate response. In addition, we will evaluate whether immunothertapy changes the late phase response and if the change is related to the efficacy of the treatment. In the future, it is hoped that the system can be expanded to study other cellular components of the inflammatory response, such as lymphocytes, macrophages, eosinophils and neutrophils, and to correlate the cellular response with the presence of inflammatory mediators. We will also study whether antigen is necessary for the initiation and/or continuation of this immunologic response. We will begin by asking the question, does a physical stimulus, cold dry air, induce a late phase response? If so, then the immunology of the late phase response is probably relevant to other inflammatory diseases in the nose and, as such, will merit the thorough study described for allergen-induced late phase response.
| Proud, D; Naclerio, R M; Gwaltney, J M et al. (1990) Kinins are generated in nasal secretions during natural rhinovirus colds. J Infect Dis 161:120-3 |
| Flowers, B K; Proud, D; Kagey-Sobotka, A et al. (1990) The effect of a leukotriene antagonist on the early response to antigen. Otolaryngol Head Neck Surg 102:219-24 |
| Naclerio, R M; Proud, D; Kagey-Sobotka, A et al. (1989) The effect of cetirizine on early allergic response. Laryngoscope 99:596-9 |
| Togias, A G; Proud, D; Kagey-Sobotka, A et al. (1989) In vivo and in vitro effects of antihistamines on mast cell mediator release: a potentially important property in the treatment of allergic disease. Ann Allergy 63:465-9 |
| Hedlin, G; Silber, G; Schieken, L et al. (1989) Attenuation of allergen sensitivity early in the course of ragweed immunotherapy. J Allergy Clin Immunol 84:390-9 |
| Baroody, F; Proud, D; Kagey-Sobotka, A et al. (1989) The effects of H1 antihistamines on the early allergic response. Ann Allergy 63:551-5 |
| Creticos, P S; Marsh, D G; Proud, D et al. (1989) Responses to ragweed-pollen nasal challenge before and after immunotherapy. J Allergy Clin Immunol 84:197-205 |
| Wachs, M; Proud, D; Lichtenstein, L M et al. (1989) Observations on the pathogenesis of nasal priming. J Allergy Clin Immunol 84:492-501 |
| Proud, D; Hendley, J O; Gwaltney, J M et al. (1989) Recent studies on the rule of kinins in inflammatory diseases of human airways. Adv Exp Med Biol 247A:117-23 |
| Walden, S M; Proud, D; Bascom, R et al. (1988) Experimentally induced nasal allergic responses. J Allergy Clin Immunol 81:940-9 |
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