IgE alone promotes human lung mast cell survival through the autocrine production of IL-6.
IgE alone promotes human lung mast cell survival through the autocrine production of IL-6.
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DOI：
10.1186/1471-2172-9-2
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发表时间：
2008-01-23
期刊：
影响因子：
3
通讯作者：
Bradding P
中科院分区：
文献类型：
--
作者：
Cruse G;Cockerill S;Bradding P
肥大细胞在哮喘中起着关键作用，最近的证据表明，在这种疾病中，肥大细胞的持续激活部分是通过在没有抗原的情况下通过IgE介导的。在这项研究中，我们研究了单用IgE是否能提高人肺肥大细胞(HLMC)的存活率。将纯化的HLMC培养4周，在有或无人骨髓瘤IgE的情况下，停用细胞因子后进行10天以上的存活分析。采用实时定量RT-PCR方法检测HLMC上清液中IL-6mRNA的表达，用ELISA法检测HLMC培养上清液中IL-6蛋白的表达。细胞因子停用后，免疫球蛋白E单独以剂量依赖的方式促进HLMC存活。加入中和的抗IL-6抗体可消除免疫球蛋白E诱导的存活，但不能通过添加中和的抗干细胞因子。IgE致敏后HLMC IL-6mRNA表达显著上调，细胞培养上清液中IL-6浓度也明显升高。这些数据综合起来表明，在缺乏抗原的情况下，IgE通过自分泌IL-6促进HLMC存活。这为IL-6和IgE在哮喘发病中的作用提供了进一步的机制，而抗IgE治疗可能通过该机制达到治疗效果。
Mast cells play a key role in asthma and recent evidence indicates that their ongoing activation in this disease is mediated, in part, via IgE in the absence of antigen. In this study we have examined whether IgE alone enhances human lung mast cell (HLMC) survival. Purified HLMC were cultured for 4 weeks and survival assays then performed over 10 days following cytokine withdrawal in the presence or absence of human myeloma IgE. Quantitative real time RT-PCR was carried out to examine IL-6 mRNA expression and IL-6 protein was measured in HLMC supernatants by ELISA. IgE alone promoted the survival of HLMC in a dose-dependent manner following cytokine withdrawal. IgE-induced survival was eliminated with the addition of neutralising anti-IL-6 antibody but not by the addition of neutralising anti-stem cell factor. IgE sensitisation initiated profound upregulation of IL-6 mRNA in HLMC, and IL-6 concentrations were also raised in the culture supernatants of IgE-exposed cells. These data taken together suggest that IgE in the absence of antigen promotes HLMC survival through the autocrine production of IL-6. This provides a further mechanism through which IL-6 and IgE contribute to the pathogenesis of asthma, and through which anti-IgE therapy might achieve its therapeutic effect.
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影响因子：
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