Activation of human lung mast cells bymonomeric immunoglobulin E
Activation of human lung mast cells bymonomeric immunoglobulin E
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DOI：
10.1183/09031936.05.00091704
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发表时间：
2005-05-01
影响因子：
24.3
通讯作者：
Bradding, P
中科院分区：
文献类型：
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作者：
Cruse, G;Kaur, D;Bradding, P
哮喘中慢性肥大细胞活化的机制尚不清楚。单体免疫球蛋白（IG）E在过敏原的情况下诱导介体从啮齿动物肥大细胞释放，表明IgE在哮喘支气管粘膜内肥大细胞的持续活化中可能起作用。本研究观察了单体IgE对人肺肥大细胞（HLMC）内钙离子内流和介质释放的诱导作用。对单个负载fura-2的细胞进行比率Ca 2+成像。用放射酶法测定组胺释放，用ELISA法测定白三烯C-4（LTC 4）和白细胞介素（IL）-8（IL-8）的含量。这与胞质游离Ca 2+的升高有关。增强组胺释放仍然明显1周后，首次暴露于IgE表明，继续暴露保持增强的secretory. Monomer免疫球蛋白E单独激活培养的人肺肥大细胞启动钙离子内流，脱粒，花生四烯酸代谢和细胞因子的合成。这些发现支持了哮喘气道内肥大细胞的免疫球蛋白E负荷有助于这种疾病的气道生理紊乱的假设。
The mechanism of chronic mast cell activation in asthma is unclear. Monomeric immunoglobulin (Ig)E in the absence of allergen induces mediator release from rodent mast cells, indicating a possible role for IgE in the continued activation of mast cells within the asthmatic bronchial mucosa. In this study it was investigated whether monomeric IgE induces Ca2+ influx and mediator release from human lung mast cells (HLMC).Purified HLMC were cultured for 4 weeks and then exposed to monomeric human myeloma IgE. Ratiometric Ca2+ imaging was performed on single fura-2-loaded cells. Histamine release was measured by radioenzymatic assay; leukotriene C-4 (LTC4) and interleukin (IL)-8 were measured by ELISA.At concentrations experienced in vivo, monomeric IgE induced dose-dependent histamine release, LTC4 production and IL-8 synthesis. This was associated with a rise in cytosolic free Ca2+. Enhanced histamine release was still evident 1 week after initial exposure to IgE suggesting that continued exposure maintains enhanced secretion.Monomeric immunoglobulin E alone activates cultured human lung mast cells initiating Ca2+ influx, degranulation, arachidonic acid metabolism and cytokine synthesis. These findings support the hypothesis that immunoglobulin E loading of mast cells within the asthmatic airway contributes to the disordered airway physiology of this disease.