Does IgE bind to and activate eosinophils from patients with allergy?
Does IgE bind to and activate eosinophils from patients with allergy?
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DOI：
10.4049/jimmunol.162.11.6901
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发表时间：
1999-06
影响因子：
4.4
通讯作者：
H. Kita;Masayuki Kaneko;K. Bartemes;D. Weiler;A. Schimming;Charles E. Reed;G. Gleich
中科院分区：
文献类型：
--
作者：
H. Kita;Masayuki Kaneko;K. Bartemes;D. Weiler;A. Schimming;Charles E. Reed;G. Gleich
据报道，人嗜酸性粒细胞同时表达高亲和力IgE受体（FcepsilonRI）的mRNA和蛋白；推测该受体在变态反应性疾病中嗜酸性粒细胞介质释放中起作用。然而，问题仍然存在。有多少FcepsilonRI蛋白实际上在嗜酸性粒细胞的细胞表面表达？如果存在，这些IgE受体是否与嗜酸性粒细胞的效应功能有关？为了解决这些问题，我们研究了豚草花粉热患者的血液嗜酸性粒细胞。通过标准的FACS分析，在嗜酸性粒细胞表面检测到高水平的低亲和力IgG受体（FcgammaRII, CD32），但未检测到FcepsilonRI的表达。然而，用生物素化的嵌合IgE （cIgE）体外致敏后，用pe结合的链亲和素检测细胞结合的cIgE。这种cIgE结合被抗FcepsilonRI单抗部分抑制，这表明嗜酸性粒细胞确实表达少量的FcepsilonRI，只有通过灵敏的方法才能检测到。事实上，全血FACS分析显示，嗜酸性粒细胞表达的FcepsilonRI约为嗜碱性粒细胞表达的0.5%。当受人IgE或抗人IgE刺激时，这些嗜酸性粒细胞不发挥效应功能；没有产生白三烯C4或超氧阴离子，也没有可检测到的脱粒反应。相比之下，嗜酸性粒细胞具有膜结合的人IgG，当受到人IgG或抗人IgG的刺激时，它们表现出功能反应。因此，IgG和/或细胞因子，如IL-5，似乎对过敏性疾病中嗜酸性粒细胞的激活比IgE更重要。
Human eosinophils have been reported to express both the mRNA and protein for the high affinity IgE receptor (FcepsilonRI); it is speculated that this receptor plays a role in eosinophil mediator release in allergic diseases. However, questions still remain. How much of the FcepsilonRI protein is actually expressed on the cell surface of the eosinophil? If they are present, are these IgE receptors associated with effector functions of eosinophils? To address these issues, we studied blood eosinophils from patients with ragweed hay fever. A high level of low affinity IgG receptor (FcgammaRII, CD32), but no expression of FcepsilonRI, was detectable on the eosinophil surface by standard FACS analysis. However, after in vitro sensitization with biotinylated chimeric IgE (cIgE), cell-bound cIgE was detected by PE-conjugated streptavidin. This cIgE binding was partially inhibited by anti-FcepsilonRI mAb, suggesting that eosinophils do express minimal amounts of FcepsilonRI detectable only by a sensitive method. Indeed, FACS analysis of whole blood showed that eosinophils express approximately 0.5% of the FcepsilonRI that basophils express. When stimulated with human IgE or anti-human IgE, these eosinophils did not exert effector functions; there was neither production of leukotriene C4 or superoxide anion nor any detectable degranulation response. In contrast, eosinophils possessed membrane-bound human IgG and showed functional responses when stimulated with human IgG or anti-human IgG. Thus, IgG and/or cytokines, such as IL-5, appear to be more important for eosinophil activation in allergic diseases than IgE.