γ-干扰素转基因对过敏原导致的小鼠肺嗜酸性粒细胞浸润的抑制作用

Inhibitory effect of IFN-γ transgene expression on allergen induced murine pulmonary eosinophil infiltration

目的 :探讨腺病毒介导的小鼠γ 干扰素在小鼠哮喘模型肺上皮细胞内的转基因表达对过敏原所致的嗜酸性粒细胞浸润的作用。方法 :C5 7小鼠经卵蛋白 (ovalbumin ,OVA)腹腔致敏和气道吸入激发建立哮喘模型 ,48h后收获小鼠肺泡灌洗液 (bronchoalveolarlavage ,BAL)和小鼠肺 ;哮喘模型在OVA激发前 48h ,在其气道内给予带有γ 干扰素的复制缺陷腺病毒 (replication deficientadenoviruswithIFN γgene,AdCMVmIFNγ) 5× 10 8空斑形成单位 (pfu) ,同上在OVA激发 48h后收获其肺泡灌洗液和肺。结果 :在卵蛋白所致的哮喘模型中 ,肺组织病理可见支气管周围、血管周围及部分肺泡内明显的嗜酸粒细胞浸润 ,肺泡灌洗液中的嗜酸粒细胞平均占 (75 .13±6 .85 ) % ,而在阴性对照组中则未见嗜酸粒细胞 ;小鼠哮喘模型气道内给予AdCMVmIFNγ后 ,肺内嗜酸粒细胞浸润的程度明显减少 ,肺泡灌洗液中的嗜酸粒细胞占 (9.0 0± 4.5 8) % (P <0 .0 0 1) ,二者均显著低于哮喘模型组。结论 :小鼠的IFN γ经腺病毒介导在小鼠肺上皮细胞内的表达可明显抑制过敏原所致的肺内嗜酸性粒细胞浸润 。

Objective: To investigate the effect of IFN γ transgene expression on allergen induced pulmonary eosinophil infiltration in murine asthmatic model. Methods: C57 mice were primed intraperitoneally and challenged by aerosol with ovalbumin (OVA) to produce asthmatic model. Bronchoalveolar lavage (BAL) and lungs were recovered after 48 hour OVA post challenge. Replication deficient adenovirus with IFN γ gene (AdCMVIFNγ) 5×10 8 plaque forming unit (pfu) was administrated intratracheally in murine asthmatic model 48 hours before OVA challenging. BAL and lungs were recovered after 48 hour OVA post challenge. Results: In asthmatic model, eosinophil infiltrated around airways and blood vessels, and partial alveolar sacs histologically, but non OVA sensitized mice showed none of these changes. The eosinophils (Eos) constituted an average of (75.13± 6.85)% in BAL, whereas no Eos were found in BAL in the negative control ( P <0.001). In AdCMVIFNγ treated asthmatic models, histologic evaluation revealed marked suppression of eosinophil peribronchial and perivascular infiltration; the recoverable Eos in BAL were an average of (9.00±4.58)%, which was statistically decreased, compared with the asthmatic control group ( P <0.001). Conclusion: IFN γ transgene expression via adenovial vector in pulmonary epithelia in vivo abrogate allergen induced eosinophilic infiltration in lungs in asthmatic model, which may provide a new therapeutic method for allergic asthma with cytokine gene transfer.