Regulatory mechanisms of eosinophil infiltration in allergic in flammation by specific immunotherapy

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An initial step of eosinophil accumulation to the allergic inflammation site is adhesion of eosinophils to vascular endothelial cells. We examined whether specific immunotherapy modifies this process via the modification of factor(s) generated from mononuclear cells. Peripheral blood mononuclear cells from mite-sensitive atopic asthmatics generated eosinophil adhesion-inducing activity in response to house dust mite. The eosinophil adhesion-inducing activity was significantly attenuated by specific immunotherapy Blocking experiments using anti-cytokine antibodies revealed that GM-CSF is involved in the development of the adhesion-inducing activity We next examined whether immunotherapy modifies the process of eosinophil transendothelial migration. The supernatants of antigen-stimulated mononuclear cells induced eosinophil transmigration across endothelial cells stimulated with IL-4 plus TNF-alpha. We observed that the transmigration activity was actually blocked by an anti-CCR3 antibody, suggesting an involvement of C-C chemokine families. Finally, we observed that the transmigration activity was significantly reduced following specific immunotherapy. These results suggest that immunotherapy attenuates antigen-dependent eosinophil accumulation to allergic inflammation site via the reduction of eosinophil adhesion to and transmigration across endothelial cells