The specific aims in this proposal will extend earlier inquires into inflammatory cell induced bronchoconstriction and airways hyperactivity in cats, a novel animal model that Dr. Padrid has developed under the guidance of Dr. Leff and Dr. Jeffrey Bluestone. There are no available animal models that duplicate the syndrome of human asthma. One major objective of this proposal is to evaluate the effects of eosinophils, T cells, and cytokines elaborated by T cells on airways reactivity in an ascaris suum-sensitized and challenged feline model of allergic asthma which shares the characteristics of 1) antigen induced bronchoconstriction, 2) airway wall inflammation, and 3) airways hyperactivity that are defining features of human allergic asthma. Using this animal model the following hypotheses will be tested (1) Eosinophils and T lymphocytes obtained by airway biopsy and bronchoalveolar lavage are activated in antigen but not sham sensitized and acutely challenged cats. (2) There is a precise temporal relationship between T cell activation, elaboration of interleukin (IL) 2, IL-4 and IL-5, influx of activated eosinophils into the airways, and development of airways hyperreactivity in this model. (3) Inhibition of T cell activation will inhibit the development of airway inflammation and airways hyperreactivity in this model. From these studies, Dr. Padrid hopes to learn how activated eosinophils and T cells influence airway responsiveness. Insight gained from this work may shed light on parallel mechanisms that may operate in human and naturally occurring feline asthma.
