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

嗜酸性粒细胞积聚到过敏性炎症部位的第一步是嗜酸性粒细胞与血管内皮细胞的粘附。我们研究了特异性免疫疗法是否通过对单个核细胞产生的因子的修饰来改变这一过程。螨敏感的特应性哮喘患者外周血单核细胞对屋尘螨产生嗜酸性粒细胞粘附诱导活性。特异性免疫治疗显著降低了嗜酸性粒细胞的粘附诱导活性，使用抗细胞因子抗体阻断实验显示GM-CSF参与了粘附诱导活性的发展，我们接下来研究了免疫治疗是否改变嗜酸性粒细胞跨内皮迁移的过程。抗原刺激的单核细胞上清液诱导嗜酸性粒细胞在IL-4 + tnf - α刺激下跨内皮细胞迁移。我们观察到，转运活性实际上被抗ccr3抗体阻断，这表明C-C趋化因子家族参与其中。最后，我们观察到特异性免疫治疗后转运活性显著降低。这些结果表明，免疫治疗通过减少嗜酸性粒细胞对内皮细胞的粘附和跨内皮细胞的迁移，减轻了抗原依赖性嗜酸性粒细胞在过敏性炎症部位的积累

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