Allergic reactions produce both immediate responses which occur in minutes as well as later responses (termed late phase reactions or LPR) which occur over a period of hours or days. Experimentally induced pulmonary LPR produce a prolonged increase in airway hyperirritability and share other clinical features seen in patients with severe asthma and cystic fibrosis. The mast cell plays a central role in the production of LPR but the precise mechanisms by which it does so are currently undetermined. We propose, therefore, to investigate mechanisms by which mast cells may induce these reactions using a rodent animal model with which we have considerable experience. We plan to isolate and characterize factor(s) from rat peritoneal mast cell granules that are capable of gnerating tissue inflammation both within rat skin and lung and to assess the ability of these factors to affect pulmonary mucous production. The biologic activity of these factors will be assessed as follows: 1) histologic analysis of in vivo ability to produce cutaneous inflammation; 2) histologic analysis of in vivo ability to produce pulmonary inflammation; 3) in vitro chemotaxis; 4) in vitro ability to affect mucous release from cultured rat trachea. The results of these studies will be important extensions of our previous work on the pathogenesis of cutaneous LPR and will provide valuable insights into the mechanisms responsible for mast cell participation in the production of chronic airway inflammation.
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