Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglobulin-E-mediated systemic anaphylaxis
Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglobulin-E-mediated systemic anaphylaxis
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DOI：
10.1016/j.immuni.2008.02.008
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发表时间：
2008-04-01
期刊：
影响因子：
32.4
通讯作者：
Karasuyama, Hajime
中科院分区：
文献类型：
--
作者：
Tsujimura, Yusuke;Obata, Kazushige;Karasuyama, Hajime
过敏反应是一种急性、严重、可能致命的全身性过敏反应。免疫球蛋白E(IgE)、肥大细胞和组胺长期以来一直与过敏反应有关，但另一种由免疫球蛋白G介导的途径被认为在诱发过敏反应中更重要。在这里，我们发现嗜碱性粒细胞是最不常见的血细胞，在IgE介导的过敏反应中是必不可少的，但在免疫球蛋白介导的、被动的和主动的全身过敏反应中起着关键作用。在体内，去除嗜碱性粒细胞，而不是巨噬细胞、中性粒细胞或NK细胞，可以改善免疫球蛋白介导的被动过敏反应，并使小鼠在主动过敏反应中免于死亡。在捕获免疫球蛋白变应原复合体后，嗜碱性粒细胞释放血小板激活因子(PAF)，导致血管通透性增加。这些结果强调了嗜碱性粒细胞在体内的关键作用，并对比了导致过敏原诱导的全身过敏反应的两条主要的、不同的途径：一条由嗜碱性粒细胞、免疫球蛋白和PAF介导，另一条由肥大细胞、IgE和组胺介导。
Anaphylaxis is an acute, severe, and potentially fatal systemic allergic reaction. Immunoglobulin E (IgE), mast cells, and histamine have long been associated with anaphylaxis, but an alternative pathway mediated by IgG has been suggested to be more important in the elicitation of anaphylaxis. Here, we showed that basophils, the least common blood cells, were dispensable for IgE-mediated anaphylaxis but played a critical role in IgG-mediated, passive and active systemic anaphylaxis in mice. In vivo depletion of basophils but not macrophages, neutrophils, or NK cells ameliorated IgG-mediated passive anaphylaxis and rescued mice from death in active anaphylaxis. Upon capture of IgG-allergen complexes, basophils released platelet-activating factor (PAF), leading to increased vascular permeability. These results highlight a pivotal role for basophils in vivo and contrast two major, distinct pathways leading to allergen-induced systemic anaphylaxis: one mediated by basophils, IgG, and PAF and the other "classical" pathway mediated by mast cells, IgE, and histamine.