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

特异性免疫疗法对过敏性炎症中嗜酸性粒细胞浸润的调节机制

• 批准号: 10670422
• 负责人: NAGATA Makoto
• 金额: $ 2.05万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670422/
• 关键词: Specific immunotherapy; eosinophils; cell adhesion; endothelial cells; trans endothelial migration; mononuclear cells; 免疫療法; VCAM-1; 気管支喘息; 単核球; サイトカイン; GM-CSF

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

嗜酸性粒细胞聚集到过敏性炎症部位的第一步是嗜酸性粒细胞粘附到血管内皮细胞。我们检查了特异性免疫疗法是否通过改变单核细胞产生的因子来改变这一过程。来自对螨敏感的特应性哮喘患者的外周血单核细胞响应屋尘螨而产生嗜酸性粒细胞粘附诱导活性。特异性免疫疗法显着减弱了嗜酸性粒细胞粘附诱导活性。使用抗细胞因子抗体的封闭实验表明，GM-CSF参与了粘附诱导活性的发展。接下来，我们检查了免疫疗法是否改变了嗜酸性粒细胞跨内皮迁移的过程。抗原刺激的单核细胞的上清液诱导嗜酸性粒细胞跨过用IL-4加TNF-α刺激的内皮细胞迁移。我们观察到，轮回活性实际上被抗 CCR3 抗体阻断，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轮回活性显着降低。这些结果表明，免疫疗法通过减少嗜酸性粒细胞与内皮细胞的粘附和跨内皮细胞的迁移来减弱抗原依赖性嗜酸性粒细胞在过敏性炎症部位的积累

项目成果

Makoto Nagata,et al.: "Effect of immunotherapy on the production of eosinophil odhesion-indncing activity from mononuclear cells in house dust-mite-sensitive bronchial asthma" Int.Arch.Allergy Immunol.117.s1. 20-23 (1998)

Makoto Nagata 等人：“免疫疗法对屋尘螨敏感支气管哮喘中单核细胞产生嗜酸性粒细胞粘附诱导活性的影响”Int.Arch.Allergy Immunol.117.s1。

永田 真, 田部一秋, 山本英明, 坂本芳雄, 松尾博司: "ダニ抗原過敏性気管支喘息における抗原特異的免疫療法の臨床的意義-疫患重症度と医療費節減におよぼす効果について-"アレルギー. 48. 1316-1321 (1999)

Makoto Nagata、Kazuaki Tabe、Hideaki Yamamoto、Yoshio Sakamoto、Hiroshi Matsuo：“蜱抗原敏感性支气管哮喘中抗原特异性免疫治疗的临床意义 - 对疾病严重程度和医疗费用节省的影响 -”过敏。 ）

永田 真, 田中弘二: "ダニ抗原過敏性気管支喘息におけるクラスター方式特異的免疫療法の臨床効果の経時的推移"アレルギー. 50. 435-439 (2001)

Makoto Nagata、Koji Tanaka：“蜱抗原敏感性支气管哮喘中簇特异性免疫疗法随时间的临床效果”过敏。 50. 435-439 (2001)

永田 真、他: "ダニ抗原過敏性成人気管支喘息における抗原特異的免疫療法の臨床的意義―疾患重症度と医療費節減におよぼす効果について―"アレルギー. 48・12. 1316-1321 (1999)

Makoto Nagata 等人：“抗原特异性免疫治疗对螨抗原过敏的成人支气管哮喘的临床意义 - 对疾病严重程度和医疗费用节省的影响 -” 过敏症 48・12。

永田 真, 田中弘二: "ダニ抗原過敏症気管支喘息におけるクラスター方式時特異的免疫療法の臨床効果の経時的推移"アレルギー. 50. 435-439 (2001)

Makoto Nagata、Koji Tanaka：“针对蜱抗原过敏的支气管哮喘的集群型时间特异性免疫疗法的临床疗效的时间趋势” 50. 435-439 (2001)。