The over all hypothesis of this application is that the endothelial cell (by expressing chemokines and adhesion molecules) plays a central role in eosinophil adhesion, activation and recruitment at sites of allergic inflammation. Therefore, the objective of this grant application is to investigate the role of individual adhesion molecules, as well as cytokines, which modulate both adhesion of eosinophils to endothelium and the growth of new blood vessels in vitro and in vivo at sites of allergic inflammation. In vivo studies of endothelium will utilize both neutralizing antibodies, as well as adhesion molecule and cytokine knockout mice, to assess the relative importance of an individual adhesion molecule or cytokine to allergen mediated angiogenesis, adhesion (fucosyl transferase VII knockout mice whose eosinophils do not express the adhesion molecule sLex), and transmigration of eosinophils (eotaxin knockout mice) across endothelium. The in vitro studies of eosinophil adhesion to endothelium will use intravital microscopy and a flow chamber to determine the role of an LDV motif contained in the alpha 4 chain of VLA-4 in mediating eosinophil rolling on endothelial adherent eosinophils.
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