Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
J Gen Virol. 2010 May;91(Pt 5):1155-63. doi: 10.1099/vir.0.017905-0. Epub 2010 Jan 13.
Adenovirus (Ad) type 7 can cause severe infection, including pneumonia, in military recruits and children. The initial inflammation is a neutrophilic interstitial infiltration with neutrophilic alveolitis. Subsequently, monocytes become evident and, finally, there is a predominantly lymphocytic infiltrate. We have established that Ad7 infection of epithelial cells stimulates release of the neutrophil chemotaxin interleukin (IL)-8, and have extended these studies to a human lung tissue model. Here, we studied cytokine responses to Ad7 in human alveolar macrophages (HAM) and our human lung tissue model. Both ELISA and RNase-protection assay (RPA) data demonstrated that, upon Ad7 infection, IP-10 and MIP-1alpha/beta are released from HAM. IP-10 and MIP-1alpha/beta protein levels were induced 2- and 3-fold, respectively, in HAM 24 h after Ad7 infection. We then investigated induction of specific cytokines in human lung tissue by RPA and ELISA. The results showed that IL-8 and IL-6 were induced 8 h after infection and, by 24 h, levels of IL-8, IL-6, MIP-1alpha/beta and MCP-1 were all increased. IP-10, a monocyte and lymphocyte chemokine, was also induced 30-fold, but only 24 h after infection. Immunohistochemistry staining confirmed that IL-8 was only released from the epithelial cells of lung slices and not from macrophages. IP-10 was secreted from both macrophages and epithelial cells. Moreover, full induction of IP-10 is likely to require participation and cooperation of both epithelial cells and macrophages in intact lung. Understanding the cytokine and chemokine induction during Ad7 infection may lead to novel ways to modulate the response to this pathogen.
腺病毒（Ad）7 型可导致新兵和儿童发生严重感染，包括肺炎。最初的炎症是中性粒细胞间质浸润伴中性粒细胞性肺泡炎。随后，单核细胞变得明显，最后主要是淋巴细胞浸润。我们已经证实，Ad7 感染上皮细胞会刺激中性粒细胞趋化因子白细胞介素（IL）-8 的释放，并将这些研究扩展到人类肺组织模型。在这里，我们研究了人肺泡巨噬细胞（HAM）和我们的人类肺组织模型对 Ad7 的细胞因子反应。ELISA 和核糖核酸酶保护分析（RPA）数据均表明，在 Ad7 感染后，IP-10 和 MIP-1alpha/beta 从 HAM 中释放。在 Ad7 感染后 24 小时，IP-10 和 MIP-1alpha/beta 的蛋白水平分别诱导了 2 倍和 3 倍。然后，我们通过 RPA 和 ELISA 研究了人肺组织中特定细胞因子的诱导。结果表明，IL-8 和 IL-6 在感染后 8 小时被诱导，到 24 小时时，IL-8、IL-6、MIP-1alpha/beta 和 MCP-1 的水平均增加。作为单核细胞和淋巴细胞趋化因子的 IP-10，在感染后 30 倍诱导，但仅在 24 小时后。免疫组织化学染色证实，IL-8 仅从肺切片的上皮细胞释放，而不从巨噬细胞释放。IP-10 由巨噬细胞和上皮细胞分泌。此外，IP-10 的完全诱导可能需要上皮细胞和巨噬细胞在完整的肺中参与和合作。了解 Ad7 感染期间细胞因子和趋化因子的诱导可能会导致调节对这种病原体反应的新方法。
