Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation
Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation
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DOI：
10.2332/allergolint.13-oa-0536
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发表时间：
2013-12-01
影响因子：
6.8
通讯作者：
Hide, Michihiro
中科院分区：
文献类型：
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作者：
Matsuo, Hiroaki;Yokooji, Tomoharu;Hide, Michihiro
背景资料：非甾体类抗炎药（NSAID），尤其是阿司匹林和食品添加剂（FA）可能会加重慢性特发性荨麻疹和食物依赖性运动诱导过敏反应（FDEIA）患者的过敏症状。这些物质增加人体肥大细胞和嗜碱性粒细胞释放组胺被推测为过敏症状加重的原因。我们试图探讨阿司匹林对IgE介导的组胺释放的作用机制。方法：非甾体抗炎药，脂肪酸或环氧合酶（考克斯）抑制剂对人嗜碱性粒细胞组胺释放的影响，通过重力分离浓缩进行了评价。结果：苯甲酸盐和柠檬黄，这没有考克斯抑制活性，增加组胺释放嗜碱性粒细胞类似阿司匹林。相反，布洛芬、美洛昔康、FR 122047和NS-398具有考克斯抑制活性，不影响组胺释放。这些结果表明，阿司匹林增加组胺释放不是由于考克斯抑制。据观察，阿司匹林增加组胺释放从人嗜碱性粒细胞只有当特异性激活的抗IgE抗体，而不是由A23187或甲酰甲硫氨酰亮氨酰苯丙氨酸。当IgE受体信号通路被激活时，阿司匹林增加了Syk的磷酸化。此外，慢性荨麻疹和FDEIA患者往往是更敏感的阿司匹林的组胺释放的增强方面，与健康controls.Conclusions：阿司匹林增强组胺释放嗜碱性粒细胞通过增加Syk激酶激活，和增强组胺释放的NSAID或FA可能是一个可能的原因，慢性荨麻疹和FDEIA患者的症状恶化。
Background: Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, and food additives (FAs) may exacerbate allergic symptoms in patients with chronic idiopathic urticaria and food-dependent exercise-induced anaphylaxis (FDEIA). Augmentation of histamine release from human mast cells and basophils by those substances is speculated to be the cause of exacerbated allergic symptoms. We sought to investigate the mechanism of action of aspirin on IgE-mediated histamine release.Methods: The effects of NSAIDs, FAs or cyclooxygenase (COX) inhibitors on histamine release from human basophils concentrated by gravity separation were evaluated.Results: Benzoate and tartrazine, which have no COX inhibitory activity, augmented histamine release from basophils similar to aspirin. In contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX inhibitory activity, did not affect histamine release. These results indicate that the augmentation of histamine release by aspirin is not due to COX inhibition. It was observed that aspirin augmented histamine release from human basophils only when specifically activated by anti-IgE antibodies, but not by A23187 or formyl-methionyl-leucylphenylalanine. When the IgE receptor signaling pathway was activated, aspirin increased the phosphorylation of Syk. Moreover, patients with chronic urticaria and FDEIA tended to be more sensitive to aspirin as regards the augmentation of histamine release, compared with healthy controls.Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.