Gauldie J, Graham F, Xing Z, Braciak T, Foley R, Sime P J
Department of Pathology, McMaster University, Hamilton, ON, Canada.
Ann N Y Acad Sci. 1996 Oct 31;796:235-44. doi: 10.1111/j.1749-6632.1996.tb32586.x.
In summary, we have been able to demonstrate that adenovirus vectors are valuable tools in examining the roles played by individual cytokines in lung responses and inflammation. These viral vectors have marked trophism for the epithelial cells of the lung and are highly efficient in transferring the genes into these lining cells. This results in significant expression of cytokines both within the lumen and the parenchyma of the lung. As a result of an individual cytokine being overexpressed, there are cytokine-specific changes seen-IL-6 resulting in lymphocytosis, MIP2 resulting in neutrophil accumulation, RANTES resulting in monocyte accumulation, TGF beta resulting in monocytosis but no fibrosis, and GM-CSF most surprisingly resulting in tissue eosinophilia, granuloma formation, and subsequently the onset of fibrosis. These vectors have helped pinpoint the role of a number of the cytokines in inducing chronic inflammatory changes to the lung and imply that a single cytokine may not be the only trigger resulting in chronic changes within the lung parenchyma.
总之，我们已经能够证明腺病毒载体是研究单个细胞因子在肺部反应和炎症中所起作用的有价值工具。这些病毒载体对肺上皮细胞具有明显的嗜性，并且在将基因转移到这些衬里细胞中效率很高。这导致细胞因子在肺腔和实质内都有显著表达。由于单个细胞因子的过度表达，会出现细胞因子特异性变化——白细胞介素-6导致淋巴细胞增多，巨噬细胞炎症蛋白-2导致中性粒细胞积聚，调节激活正常T细胞表达和分泌的趋化因子导致单核细胞积聚，转化生长因子β导致单核细胞增多但无纤维化，而粒细胞-巨噬细胞集落刺激因子最令人惊讶的是导致组织嗜酸性粒细胞增多、肉芽肿形成，随后出现纤维化。这些载体有助于确定多种细胞因子在诱导肺部慢性炎症变化中的作用，并表明单一细胞因子可能不是导致肺实质内慢性变化的唯一触发因素。
