Basophils are essential initiators of a novel type of chronic allergic inflammation
Basophils are essential initiators of a novel type of chronic allergic inflammation
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DOI：
10.1182/blood-2007-01-068718
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发表时间：
2007-08-01
期刊：
影响因子：
20.3
通讯作者：
Karasuyama, Hajime
中科院分区：
文献类型：
--
作者：
Obata, Kazushige;Mukai, Kaori;Karasuyama, Hajime
嗜碱性粒细胞占外周血白细胞的不到1%，通常被认为是次要的，可能是多余的循环肥大细胞。最近的发现，嗜碱性粒细胞容易产生大量的辅助性T细胞2（Th 2）细胞因子，如IL-4提供了新的见解嗜碱性粒细胞在过敏性疾病和免疫病原体的可能作用。然而，对嗜碱性粒细胞的深入研究，特别是它们在体内的功能，一直受到缺乏适当的动物模型，如突变动物缺乏嗜碱性粒细胞的阻碍。在这里，我们建立了一个单克隆抗体，与小鼠嗜碱性粒细胞反应，并在体内给药时耗尽它们。小鼠的mAb治疗对经典过敏反应（如被动皮肤过敏反应和接触性超敏反应）未显示任何显著影响。相反，它完全消除了IgE介导的慢性过敏性皮炎的发展，其特征是大量嗜酸性粒细胞浸润，即使嗜碱性粒细胞仅占浸润的约2%。皮炎进展期间的治疗导致浸润性嗜酸性粒细胞和中性粒细胞数量急剧减少，同时从皮肤病变中消除嗜碱性粒细胞。因此，嗜碱性粒细胞在IgE介导的慢性变应性炎症的发展中起着关键作用，作为启动者而不是效应者。
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 IgIE-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 IgEmediated chronic allergic inflammation, as an initiator rather than as an effector.