以氣喘的小鼠模式研究CD95 Ligand基因在呼吸道發炎及免疫調節細胞的影響

過敏性氣喘病的特徵包括呼吸道過度反應(airway hyperresponsiveness)、血液中免疫球蛋白E的含量升高、呼吸道發炎細胞主要是嗜酸性白血球及分泌Th2細胞激素的T 細胞大量浸潤。Th2細胞在氣喘致病及進程上均扮演重要的角色。如同其他免疫反應的終止，肺部發炎反應的消除亦憑藉Fas-FasL引起細胞凋亡(apoptosis)作用而移除不再需要之發炎細胞。臨床研究顯示氣喘病與肺部的發炎細胞例如嗜酸性白血球及淋巴球的細胞凋亡能力降低有關。已知Fas ligand 屬於tumor necrosis factor家族的一員，當它與其接受器Fas 結合，會引起帶有Fas的細胞進行細胞凋亡。在此研究中，我們欲探討是否引起細胞凋亡對於氣喘病的緩解是有幫助的以及利用氣喘的小鼠模式來研究CD95 Ligand基因對於呼吸道發炎及免疫調節細胞的影響。我們以重組腺病毒載體表現FasL (Ad-FasL)及以攜帶FasL之腺病毒感染使之表現FasL之樹突細胞 (DC-FasL) 打入過敏小鼠體內後再測量其氣喘特徵的變化。我們的研究結果顯示OVA致敏小鼠以氣管內注射Ad-FasL後，呼吸道過度反應及嗜酸性白血球過多症(eosinophilia)明顯的降低,可能藉由直接造成嗜酸性白血球的細胞凋亡或影響嗜酸性白血球的趨化因子分泌細胞間接降低嗜酸性白血球浸潤的數目而產生效果。同時浸潤的淋巴球的數目減少且Th2細胞激素包括IL-5和IL-13均減少；發炎因子KC、TNF-

關鍵字

樹突細胞, OVA特異性T 細胞,腺病毒載體, 細胞凋亡,嗜酸性白血球

並列摘要

Allergic asthma is characterized by airway hyperresponsiveness, high serum IgE levels, and cellular infiltration of the airway with predominantly eosinophils and T cells expressing a type 2 T helper (Th2) profile of cytokines. Th2 cells are crucial for the initiation and progression of allergic asthma. The normal resolution of inflammation in the lung occurs through the regulated removal of unneeded cells by Fas-Fas ligand mediated apoptosis. Asthmatics are found to be associated with reduced apoptosis of inflammatory cells such as eosinophils and lymphocytes in the lung. Fas ligand (FasL) is a member of the tumor necrosis factor family, and when bound to Fas, it induces apoptosis of the cells. In the present study, we attempted to clarify whether the induction of apoptosis is beneficial in asthma and to examine the effect of FasL gene on airway inflammation and immune effector cells in allergic asthma. To this end, recombinant adenovirus expressing murine FasL (Ad-FasL) and dendritic cells (DC) genetically engineered to express FasL (DC-FasL) were delivered into allergic mice and asthma manifestations were measured. We found that a single intratracheally administration of Ad-FasL in OVA-immunized mice significantly alleviated airway hyperresponsiveness and eosinophilia by inducing the apoptosis of eosinophils and/or reducing eosinophil attractant factors, such as IL-5 and eotaxin levels. The number of infiltrated lymphocytes and Th2 cytokines, including IL-5 and IL-13, decreased in OVA-immunized mice by administration of Ad-FasL. KC and TNF-

並列關鍵字

dendritic cell, OVA-specific T cells, adenoviral v

參考文獻

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以氣喘的小鼠模式研究CD95 Ligand基因在呼吸道發炎及免疫調節細胞的影響

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