气道平滑肌中自身上调的Fc受体表达及作用介导了其在特应性哮喘致敏状态下反应性的改变。
Autologously up-regulated Fc receptor expression and action in airway smooth muscle mediates its altered responsiveness in the atopic asthmatic sensitized state.
作者信息
Hakonarson H, Grunstein M M
机构信息
Division of Pulmonary Medicine, The Joseph Stokes, Jr., Research Institute, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5257-62. doi: 10.1073/pnas.95.9.5257.
To elucidate the role of IgE-dependent mechanisms in inducing altered airway responsiveness in the atopic asthmatic state, the expression and actions of Fc receptor activation were examined in isolated rabbit tracheal smooth muscle (TSM) tissue and cultured cells passively sensitized with sera from atopic asthmatic patients or nonatopic/nonasthmatic (control) subjects. Relative to control tissues, the atopic asthmatic-sensitized TSM exhibited significantly increased maximal isometric contractility to acetylcholine (P < 0. 01) and attenuated maximal relaxation responses and sensitivity (i.e.,-log ED50) to isoproterenol (P < 0.005). These changes in agonist responsiveness in atopic sensitized TSM were ablated by pretreating the tissues with a blocking mAb to the low affinity receptor for IgE, FcepsilonRII (i.e., CD23) or by depleting the sensitizing serum of its immune complexes. Moreover, in complimentary experiments, exogenous administration of IgE immune complexes to naive TSM produced changes in agonist responsiveness that were qualitatively similar to those obtained in the atopic asthmatic-sensitized state. Extended studies further demonstrated that, in contrast to their respective controls, atopic asthmatic serum-sensitized human and rabbit TSM tissue and cultured cells exhibited markedly induced mRNA and cell surface expression of FcepsilonRII, whereas constitutive expression of the IgG receptor subtype, FcgammaRIII, was unaltered. Finally, the up-regulated mRNA expression of FcepsilonRII observed following exposure of TSM to atopic asthmatic serum or to exogenously administered IgE immune complexes was significantly inhibited by pretreating the tissues or cells with anti-CD23 mAb. Collectively, these observations provide evidence demonstrating that the altered agonist responsiveness in atopic asthmatic sensitized airway smooth muscle is largely attributed to IgE-mediated induction of the autologous expression and activation of FcepsilonRII receptors in the airway smooth muscle itself.
为阐明IgE依赖机制在特应性哮喘状态下诱导气道反应性改变中的作用，我们在分离的兔气管平滑肌（TSM）组织以及用特应性哮喘患者或非特应性/非哮喘（对照）受试者血清被动致敏的培养细胞中，检测了Fc受体激活的表达及作用。与对照组织相比，特应性哮喘致敏的TSM对乙酰胆碱的最大等长收缩力显著增加（P<0.01），而对异丙肾上腺素的最大舒张反应和敏感性（即-log ED50）减弱（P<0.005）。用针对IgE低亲和力受体FcepsilonRII（即CD23）的阻断单克隆抗体预处理组织，或去除致敏血清中的免疫复合物，可消除特应性致敏TSM中激动剂反应性的这些变化。此外，在补充实验中，向未致敏的TSM外源性给予IgE免疫复合物，产生的激动剂反应性变化在性质上与特应性哮喘致敏状态下获得的变化相似。进一步的研究表明，与各自的对照相比，特应性哮喘血清致敏的人和兔TSM组织及培养细胞中，FcepsilonRII的mRNA和细胞表面表达明显诱导增加，而IgG受体亚型FcgammaRIII的组成性表达未改变。最后，用抗CD23单克隆抗体预处理组织或细胞，可显著抑制TSM暴露于特应性哮喘血清或外源性给予的IgE免疫复合物后观察到的FcepsilonRII mRNA表达上调。总体而言，这些观察结果提供了证据，表明特应性哮喘致敏气道平滑肌中激动剂反应性的改变很大程度上归因于IgE介导的气道平滑肌自身FcepsilonRII受体自体表达和激活。
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