and specific aims): Asthma is characterized pathologically by airways inflammation and physiologically by airways obstruction and hyperresponsiveness. The cellular infiltrate in asthma is pleomorphic, and includes T lymphocytes, eosinophils and mast cells. The mechanism of eosinophil recruitment and the development of airways hyperresponsiveness remain to be fully established. This application proposes to study the regulation of chemokine expression and the role of T cells, eosinophils and humoral responses in a murine model of allergic asthma.
The specific aims are: 1) To determine if antigen-specific T cell lines and clones can induce eotaxin production by endothelial and epithelial cell lines in vitro. 2) To determine the effect of anti-T cell and anti-cytokine interventions in vivo, on the expression of eosinophil-specific chemokines. 3) To determine the effect of neutralizing eotaxin in vivo, on antigen-induced pulmonary eosinophilia and airways hyperresponsiveness in a murine model of antigen-induced pulmonary eosinophilia. 4) To differentiate the respective roles of humoral vs. T cell-mediated responses on the expression of eosinophil-specific chemokines, pulmonary eosinophilia and airways hyperresponsiveness in a murine model of antigen-induced pulmonary eosinophilia.
| MacLean, J A; De Sanctis, G T; Ackerman, K G et al. (2000) CC chemokine receptor-2 is not essential for the development of antigen-induced pulmonary eosinophilia and airway hyperresponsiveness. J Immunol 165:6568-75 |
| De Sanctis, G T; MacLean, J A; Qin, S et al. (1999) Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammation. J Clin Invest 103:507-15 |
