Adenosine plays an important role in the pathogenesis of allergic asthma. Although multiple adenosine receptor subtype that mediates allergic asthma is the subject of controversy. The principal investigator now proposes to utilize knockoutmice deficient in each of adenosine A2a, A2b and A3 receptor expression to determine the receptor subtype involved in allergic pulmonary inflammation. The signal transduction pathway activated by adenosine receptor in mast cells derived from normal and adenosine receptor knockout mice will also be tested. The hypothesis that presence of airway inflammation induces a pulmonary mast cell hyperesponsiveness to adenosine, will be characterized in vitro by increased histamine release from mast cells an in vivo by adenosine-induced bronchospasm. These experiments will also be performed in mouse model of asthma in adenosine receptor deficient mice. The role of mast cells in these responses will also be tested by performing these experiments in mast cell deficient mice. Biochemical and molecular biology techniques will be utilized to determine whether PI3 kinase regulates mast cell degranulation but not cytokine release or leukotriene production.
| Marquardt, D L; Walker, L L (2000) Dependence of mast cell IgE-mediated cytokine production on nuclear factor-kappaB activity. J Allergy Clin Immunol 105:500-5 |
| Jagels, M A; Hugli, T E (2000) Mixed effects of TGF-beta on human airway epithelial-cell chemokine responses. Immunopharmacology 48:17-26 |
