The principal objective of this project is to determine the effect that exposure of the lung to specific antigen has on bronchopulmonary function in the immunologically-sensitized dog. The project is based upon previous studies in sensitized animals and combines the use of physiologic, pharmacologic and biochemical approaches to investigate the mechanisms through which these changes in airway function occur. Our working hypothesis is that repeated antigen exposure modifies airway function by altering the profile of mediators, specifically those derived from arachidonic acid (i.e. eicosanoids), which are synthesized within the airway tissues. Whether this alteration is due to changes in metabolism within existing airway cells or do to the antigen-induced influx of new cells, is not known. Specifically, the research will a) determine the role of eicosanoids in the acute bronchospasm of antigen challenge, b) investigate the effects of repeated antigen exposure on eicosanoid synthesis, in vivo, c) investigate the activity of enzymes of the eicosanoid metabolic pathway in microsomal preparations of airway tissues from repeatedly exposed and control dogs, as well as in specific cells isolated from the lungs of these animals, and d) determine the effects of repeated antigen exposure on non-specific airways reactivity in vivo and on the contractile reactivity of lung tissues, in vitro. The proposed studies therefore represent a multidisciplined approach to the influence of antigen exposure on lung function in that they will utilize in vivo and in vitro techniques to correlate changes in physiologic functions with underlying biochemical mechanisms at various levels of the tracheobronchial tree. It is anticipated that these studies will provide useful new information about mediator metabolism in the airways of the allergic lung.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Respiratory and Applied Physiology Study Section (RAP)
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Johns Hopkins University
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Takahashi, N; Yu, X Y; Schofield, B H et al. (1995) Expression of ICAM-1 in airway epithelium after acute ozone exposure in the mouse. J Appl Physiol 79:1753-61
Yu, X Y; Schofield, B H; Croxton, T et al. (1994) Physiologic modulation of bronchial epithelial cell barrier function by polycationic exposure. Am J Respir Cell Mol Biol 11:188-98
Takahashi, N; Liu, M C; Proud, D et al. (1994) Soluble intracellular adhesion molecule 1 in bronchoalveolar lavage fluid of allergic subjects following segmental antigen challenge. Am J Respir Crit Care Med 150:704-9
Yu, X Y; Hubbard, W; Spannhake, E W (1992) Inhibition of canine tracheal smooth muscle by mediators from cultured bronchial epithelial cells. Am J Physiol 262:L229-34
Ninomiya, H; Yu, X Y; Hasegawa, S et al. (1992) Endothelin-1 induces stimulation of prostaglandin synthesis in cells obtained from canine airways by bronchoalveolar lavage. Prostaglandins 43:401-11
Turner, C R; Spannhake, E W (1990) Acute topical steroid administration blocks mast cell increase and the late asthmatic response of the canine peripheral airways. Am Rev Respir Dis 141:421-7
Yoss, E B; Spannhake, E W; Flynn, J T et al. (1990) Arachidonic acid metabolism in normal human alveolar macrophages: stimulus specificity for mediator release and phospholipid metabolism, and pharmacologic modulation in vitro and in vivo. Am J Respir Cell Mol Biol 2:69-80
Turner, C R; Darowski, M J; Sampson, H A et al. (1989) Dermal mast cell releasability and end organ responsiveness in atopic and nonatopic dogs. J Allergy Clin Immunol 83:643-8
Turner, C R; Kolbe, J; Spannhake, E W (1988) Rapid increase in mast cell numbers in canine central and peripheral airways. J Appl Physiol 65:445-51
Beckett, W S; Black, C; Turner, C et al. (1988) In vivo exposure to ozone causes increased in vitro responses of small airways. Am Rev Respir Dis 137:1236-8

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