Suzukawa Maho, Hirai Koichi, Iikura Motoyasu, Nagase Hiroyuki, Komiya Akiko, Yoshimura-Uchiyama Chitose, Yamada Hirokazu, Ra Chisei, Ohta Ken, Yamamoto Kazuhiko, Yamaguchi Masao
Department of Allergy and Rheumatology and.
Int Immunol. 2005 Sep;17(9):1249-55. doi: 10.1093/intimm/dxh301. Epub 2005 Aug 15.
Local accumulation of basophils at inflammatory sites is observed in experimental antigen challenge and in allergic diseases. It is not fully known what factor(s) regulates local basophil influx in tissues, and it has not been determined whether antigens belong in a panel of basophil chemoattractants. This study was designed to elucidate whether IgE- and high-affinity receptor for IgE (FcepsilonRI)-mediated stimulation can induce human basophil migration. The migration-inducing potency of an anti-FcepsilonRI alpha-chain mAb, CRA-1, was examined on human basophils. CRA-1 mAb elicited significant migration of basophils. The migration-inducing potency of this mAb was maximal at 100 ng ml-1, and CRA-1 mAb at 100 ng ml-1 attracted approximately 10% of total inoculated basophils above baseline levels after incubation for 2.5 h. Checkerboard analysis indicated that basophil migration induced by this mAb was mainly chemotactic and partially chemokinetic. An antigen, Der f 2, also induced migration of basophils from Der f-sensitive subjects. Basophils mixed with 1 ng ml-1 of CRA-1 mAb showed an exaggerated migration response to eotaxin, indicating that FcepsilonRI cross-linkage enhances basophil migration to other chemoattractants. Induction of basophil migration by IgE- and FcepsilonRI-cross-linking stimulation may, at least in part, explain the pathogenesis of local basophil accumulation clinically observed in allergic diseases such as asthma.
在实验性抗原攻击和过敏性疾病中,可观察到嗜碱性粒细胞在炎症部位的局部聚集。目前尚不完全清楚是什么因素调节组织中嗜碱性粒细胞的局部流入,也未确定抗原是否属于嗜碱性粒细胞趋化因子。本研究旨在阐明IgE和IgE高亲和力受体(FcepsilonRI)介导的刺激是否能诱导人嗜碱性粒细胞迁移。检测了抗FcepsilonRIα链单克隆抗体CRA-1对人嗜碱性粒细胞的迁移诱导能力。CRA-1单克隆抗体可引起嗜碱性粒细胞的显著迁移。该单克隆抗体的迁移诱导能力在100 ng/ml时最大,孵育2.5小时后,100 ng/ml的CRA-1单克隆抗体吸引了约10%接种的嗜碱性粒细胞超过基线水平。棋盘分析表明,该单克隆抗体诱导的嗜碱性粒细胞迁移主要是趋化性的,部分是化学动力学的。抗原Der f 2也可诱导Der f敏感受试者的嗜碱性粒细胞迁移。与1 ng/ml CRA-1单克隆抗体混合的嗜碱性粒细胞对嗜酸性粒细胞趋化因子显示出夸张的迁移反应,表明FcepsilonRI交联增强了嗜碱性粒细胞向其他趋化因子的迁移。IgE和FcepsilonRI交联刺激诱导嗜碱性粒细胞迁移可能至少部分解释了在哮喘等过敏性疾病中临床上观察到的局部嗜碱性粒细胞聚集的发病机制。