Serum IgE level drives basophil and mast cell IgE receptor display.
Serum IgE level drives basophil and mast cell IgE receptor display.
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血清 IgE 水平驱动嗜碱性粒细胞和肥大细胞 IgE 受体显示。
DOI：
10.1159/000237504
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发表时间：
1997
影响因子：
2.8
通讯作者：
Lichtenstein,LM
中科院分区：
文献类型：
--
作者：
MacGlashanJr,DW;Bochner,BS;Adelman,DC;Jardieu,PM;Togias,A;Lichtenstein,LM
大约20年前，我们获得了图1所示的数据，证明血清IgE水平与人嗜碱性粒细胞表面IgE受体数量之间存在极其密切的相关性[1]。当时，我们假设这种关系的存在，要么是因为两者都是遗传决定和连锁的，要么更可能是血清IgE水平决定了IgE受体的数量。我们进行了实验来验证这一假设，但在发现IL-3作为嗜碱性粒细胞生长因子之前，不可能使嗜碱性粒细胞存活超过24小时。在这一时间范围内，嗜碱性粒细胞IgE受体的数量并没有随着液相IgE浓度的变化而变化。在过去的5-8年里，特异性抗人IgE的人源化单克隆抗体已经被开发出来用于治疗目的。这些抗体针对IgE分子中与IgE受体结合的部分[2，3]。这个概念是这样的抗体将结合血清IgE，并最终消除它，而不交联嗜碱性粒细胞和肥大细胞上的IgE，从而激活它们。最近的研究，首先在体外[2，4]，然后在体内[4]，已经证明，这些抗体并没有，事实上，引起组胺的释放。在哮喘个体中进行的临床研究表明，在相对较低的浓度下，抗IgE抗体可降低血清IgE水平，同时降低对相关抗原的支气管激发的急性和晚期反应[5]。随后，我们与Genentech的研究人员合作进行了一项临床研究，其中15名对粉尘螨过敏的受试者每两周静脉注射抗IgE抗体，剂量为0.015或0.03 mg/kg/IU/ml，持续3个月。
Almost 20 years ago, we generated the data shown in figн ure 1which demonstrate the extremely close correlation beн tween the serum IgE level and the number of receptors for IgE on the surface of human basophils [1]. At that time, we hypothesized that this relationship existed either because both were genetically determined and linked or, more likely, that the serum IgE level determined the number of IgE reн ceptors. We carried out experiments to test this hypothesis but, in the era before the discovery of IL-3 as a basophil growth factor, it was impossible to keep basophils alive for more than about 24 h. In that time frame, there was no change in basophil IgE receptor number based on the fluidphase IgE concentration.Within the last 5-8 years, humanized monoclonal antiн bodies specific for human IgE have been developed for therн apeutic purposes. These antibodies are directed at that porн tion of the IgE molecule which binds to the IgE receptor [2, 3]. The concept was that such an antibody would bind to serum IgE and eventually eliminate it without cross-linking the IgE on basophils and mast cells, thereby activating them. Recent studies, first in vitro [2, 4] and then in vivo [4], have demonstrated that these antibodies did not, in fact, cause the release of histamine. Clinical studies in asthmatic individuн als with the anti-IgE, at a relatively low concentration, demн onstrated a decrease in the serum IgE level together with a reduction in both the acute and late response to bronchial provocation with relevant antigens [5]. Subsequently, we collaborated with investigators from Genentech in a clinical study in which 15 subjects allergic to Dermatophagoidesfarinae were given biweekly intravenous anti-IgE at a dose of either 0.015 or 0.03 mg/kg/IU/ml for 3 months.