Histamine-releasing factor and immunoglobulins in asthma and allergy.
Histamine-releasing factor and immunoglobulins in asthma and allergy.
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DOI：
10.4168/aair.2014.6.1.6
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发表时间：
2014-01
期刊：
影响因子：
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通讯作者：
Kawakami Y
中科院分区：
文献类型：
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作者：
Kawakami T;Kashiwakura J;Kawakami Y
人们已经对能够诱导嗜碱性粒细胞释放组胺的因素进行了30多年的研究。1995年，一种名为组胺释放因子（HRF）的蛋白质被纯化并进行了分子克隆。HRF可刺激IgE致敏的嗜碱性粒细胞和肥大细胞释放组胺和产生IL-4和IL-13。HRF样活动被发现在体液中的后期阶段的过敏反应，暗示HRF过敏性疾病。然而，HRF在过敏性疾病中的作用的确切证据仍然难以捉摸。另一方面，我们发现了单体IgE对肥大细胞的存活和活化的影响，而不涉及特异性抗原，以及IgE在其引起这种影响的能力中的异质性。IgE分子的后一种性质似乎与IgE的异质性相似，即它们能够引发嗜碱性粒细胞对HRF的反应。这种相似性导致我们最近发现，约30%的IgE分子可以通过与HRF分子内的两个结合位点的Fab相互作用与HRF结合。阻断HRF-IgE相互作用的肽抑制剂的使用揭示了HRF在促进皮肤过敏和气道炎症中的重要作用。这篇综述总结了这一发现和最近的发现，并提供了一个关于它们如何影响我们对过敏发病机制的理解和潜在改变过敏性疾病的治疗的观点。
Factors that can induce the release of histamine from basophils have been studied for more than 30 years. A protein termed histamine-releasing factor (HRF) was purified and molecularly cloned in 1995. HRF can stimulate histamine release and IL-4 and IL-13 production from IgE-sensitized basophils and mast cells. HRF-like activities were found in bodily fluids during the late phase of allergic reactions, implicating HRF in allergic diseases. However, definitive evidence for the role of HRF in allergic diseases has remained elusive. On the other hand, we found effects of monomeric IgE on the survival and activation of mast cells without the involvement of a specific antigen, as well as heterogeneity of IgEs in their ability to cause such effects. The latter property of IgE molecules seemed to be similar to the heterogeneity of IgEs in their ability to prime basophils in response to HRF. This similarity led to our recent finding that ~30% of IgE molecules can bind to HRF via their Fab interactions with two binding sites within the HRF molecule. The use of peptide inhibitors that block HRF-IgE interactions revealed an essential role of HRF to promote skin hypersensitivity and airway inflammation. This review summarizes this and more recent findings and provides a perspective on how they impact our understanding of allergy pathogenesis and potentially change the treatment of allergic diseases.