Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Front Immunol. 2022 Sep 28;13:994823. doi: 10.3389/fimmu.2022.994823. eCollection 2022.
Urticaria is characterized by the occurrence of wheals and flares in response to vasoactive mediators, such as histamine. Various studies have suggested the involvement of basophils in the pathogenesis of chronic spontaneous urticaria (CSU). However, histamine release from peripheral basophils in response to stimuli acting on the high affinity IgE receptor (FcϵRI) is impaired in many patients with CSU (non/low responders). We previously demonstrated that tissue factor (TF)s expressed on vascular endothelial cells in response to a combination of various stimuli, such as that of histamine and lipopolysaccharide (LPS), activates the extrinsic coagulation pathway and produces anaphylatoxin, complement 5a (C5a), which then activates basophils and mast cells the C5a receptor (C5aR). We have revealed that histamine release was induced in response to C5a and formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), regardless of the response to anti-IgE antibody, the reduced numbers of basophils and severity of urticaria. Moreover, we found that spontaneous release of histamine from basophils of patients with CSU is higher than that from healthy individuals. These results suggest that basophils and the complement system, which could be activated by coagulation factors, may play a critical role in the pathogenesis of CSU, especially in cases refractory to treatment involving the IgE/FcϵRI pathway.
荨麻疹的特征是在血管活性介质（如组胺）的作用下出现风团和潮红。多项研究表明，嗜碱性粒细胞参与了慢性自发性荨麻疹（CSU）的发病机制。然而，在许多 CSU 患者（无/低反应者）中，外周嗜碱性粒细胞对作用于高亲和力 IgE 受体（FcϵRI）的刺激物的组胺释放受损。我们之前证明，血管内皮细胞在各种刺激物（如组胺和脂多糖[LPS]）的组合作用下表达组织因子（TF），激活外源性凝血途径并产生过敏毒素、补体 5a（C5a），然后激活嗜碱性粒细胞和肥大细胞的 C5a 受体（C5aR）。我们已经揭示，无论对抗 IgE 抗体的反应、嗜碱性粒细胞数量减少和荨麻疹的严重程度如何，C5a 和甲酰基-L-甲硫氨酸-L-亮氨酸-L-苯丙氨酸（fMLP）均可诱导组胺释放。此外，我们发现 CSU 患者的嗜碱性粒细胞自发性释放组胺的水平高于健康个体。这些结果表明，嗜碱性粒细胞和补体系统可能通过凝血因子激活，在 CSU 的发病机制中发挥关键作用，特别是在 IgE/FcϵRI 途径治疗无效的情况下。
