哮喘联盟

   摘要
   关于诱导嗜碱性粒细胞释放组胺因子的研究已有30多年。1995年提纯和分子克隆出一种称之为组胺释放因子(HRF)的蛋白质。HRF可以刺激组胺的释放以及IgE敏感性嗜碱性粒细胞和肥大细胞生成IL-4和IL-3。在过敏反应迟发相的体液中发现有类HRF激活反应，暗示HRF存在于变应性疾病中。然而，关于HRF在变应性疾病中的作用一直缺乏确切的证据。另一方面，我们发现了单体IgE对于无特定抗原介入的存活和活化的肥大细胞的影响，以及在导致该影响能力中IgEs的异质性。后者IgE分子的性质似乎与在嗜碱性粒细胞对HRF的反应中IgEs的异质性相似。基于该相似性我们近期发现，约30%的IgE分子可以通过其Fab段与HRF分子内两个结合位点的相互作用而与HRF结合。阻断HRF-IgE相互作用的肽抑制剂的使用提示了HRF在促进皮肤超敏反应以及气道炎症中的重要作用。本综述概述了这一点以及更多最新的研究结果，并提供了一个观点，关于他们如何影响我们对变态反应发病机理的认知，并可能改变变应性疾病的治疗。

                                                                                （林江涛 审校）

Allergy Asthma Immunol Res. 2014 Jan;6(1):6-12. Epub 2013 Jul 2.


 

Histamine-Releasing Factor and Immunoglobulins in Asthma and Allergy.

Kawakami T1, Kashiwakura JI2, Kawakami Y3.

Abstract
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.
 

Allergy Asthma Immunol Res. 2014 Jan;6(1):6-12. Epub 2013 Jul 2.