Obata Kazushige, Mukai Kaori, Tsujimura Yusuke, Ishiwata Kenji, Kawano Yohei, Minegishi Yoshiyuki, Watanabe Naohiro, Karasuyama Hajime
Department of Immune Regulation, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Blood. 2007 Aug 1;110(3):913-20. doi: 10.1182/blood-2007-01-068718. Epub 2007 Apr 4.
Basophils represent less than 1% of peripheral blood leukocytes and have often been considered as minor and possibly redundant circulating mast cells. The recent finding that basophils readily generate large quantities of T helper 2 (Th2) cytokines such as IL-4 provided new insights into the possible role of basophils in allergic disorders and immunity to pathogens. However, in-depth studies on basophils, particularly their functions in vivo, have been hampered by the lack of appropriate animal models, such as mutant animals deficient only in basophils. Here, we established a mAb that reacted with mouse basophils and depleted them when administered in vivo. The mAb treatment of mice did not show any significant effect on classical allergic reactions such as passive cutaneous anaphylaxis and contact hypersensitivity. In contrast, it completely abolished the development of IgE-mediated chronic allergic dermatitis that is characterized by massive eosinophil infiltration, even though basophils accounted for only approximately 2% of the infiltrates. The treatment during the progression of the dermatitis resulted in drastic reduction in numbers of infiltrating eosinophils and neutrophils, concomitantly with elimination of basophils from the skin lesions. Thus, basophils play a pivotal role in the development of IgE-mediated chronic allergic inflammation, as an initiator rather than as an effector.
嗜碱性粒细胞在外周血白细胞中所占比例不到1%，常被视为次要且可能多余的循环肥大细胞。最近发现嗜碱性粒细胞能轻易产生大量辅助性T细胞2（Th2）细胞因子，如白细胞介素-4，这为嗜碱性粒细胞在过敏性疾病和病原体免疫中的可能作用提供了新的见解。然而，由于缺乏合适的动物模型，如仅缺乏嗜碱性粒细胞的突变动物，对嗜碱性粒细胞的深入研究，尤其是它们在体内的功能研究受到了阻碍。在此，我们制备了一种与小鼠嗜碱性粒细胞反应并在体内给药时使其耗竭的单克隆抗体。对小鼠进行单克隆抗体治疗对被动皮肤过敏反应和接触性超敏反应等经典过敏反应没有显著影响。相反，它完全消除了以大量嗜酸性粒细胞浸润为特征的IgE介导的慢性过敏性皮炎的发展，尽管嗜碱性粒细胞仅占浸润细胞的约2%。在皮炎进展过程中进行治疗导致浸润的嗜酸性粒细胞和中性粒细胞数量大幅减少，同时从皮肤病变中清除了嗜碱性粒细胞。因此，嗜碱性粒细胞在IgE介导的慢性过敏性炎症的发展中起关键作用，作为启动者而非效应器。
