CYTOMEGALOVIRUS ACTIVATION OF VASCULAR CELL SIGNALING

血管损伤是许多肺部疾病的重要因素。 例如急性呼吸窘迫综合征(ARDS)。增强版 血管平滑肌的增殖是血管病变的特征。 与肺动脉高压有关的疾病，以及 动脉硬化。更微妙的亚致命性伤害 血管形成可能与病毒感染有关。血管病毒感染 由疱疹病毒引起的细胞，如巨细胞病毒(CMV)，可能代表 激活这些细胞参与器官特异性的独特方式 黏附分子的表达对炎性细胞的募集 和细胞因子，局部组织损伤和刺激的放大 通过释放生长因子促进平滑肌细胞的增殖。 这个项目的目的是测试疱疹病毒 血管细胞体外感染导致细胞内 激活特定的信号转导通路，如核 核因子-kB和/或酪氨酸激酶的活性。后果是什么？ 信号转导激活对细胞基因表达的影响 IL-1、IL-6、TNF-a等促炎细胞因子与生长 基本成纤维细胞生长因子等因素将通过Northern blotting和 荧光素酶检测。特定蛋白质产品的生产将是 用酶联免疫吸附试验测定。这些物种在地球上的生物活性 病毒感染的血管细胞的特定培养液的条件 在生物测试中测量，例如目标平滑肌细胞的有丝分裂， 对单核/巨噬细胞和中性粒细胞黏附的影响 病毒感染的内皮细胞。细胞黏附的表达 巨细胞病毒感染内皮细胞上的分子将通过Flow进行评估 细胞学。细胞因子的激活模式将与 回收的肺泡巨噬细胞产生细胞因子 骨髓移植患者的支气管肺泡灌洗液 肺炎，合并和不合并巨细胞病毒感染，以及正常 体外感染巨细胞病毒的肺泡巨噬细胞发生 对血管系统与炎症相互作用的认识 细胞。这些数据将有助于确定其分子机制 病毒感染诱导的血管激活，这可能是重要的 了解临床疾病，如巨细胞病毒性骨炎 骨髓移植受者。

Vascular injury is an important element in a number of lung disorders such as the acute respiratory distress syndrome (ARDS). Enhanced proliferation of vascular smooth muscle is a characteristic feature in diseases associated with pulmonary hypertension, as well as in atherosclerosis. More subtle forms of sublethal injury to the vasculature may occur with viral infections. Viral infection of vascular cells by herpesviruses, such as cytomegalovirus (CMV), may represent a unique way of activating these cells to participate in the organ-specific recruitment of inflammatory cells via expression of adhesion molecules and cytokines, the amplification of local tissue injury and stimulation of smooth muscle cell proliferation via the release of growth factors. This project is designed to test the hypothesis that herpesviral infection of vascular cells in vitro results in the intracellular activation of specific signal transduction pathways such as nuclear factor NF-kB and/or the activity of tyrosine kinases. The consequences of signal transduction activation on the expression of cellular genes for proinflammatory cytokines such as IL-1, IL-6, and TNF-a and growth factors such as basic FGF will be assessed via Northern blotting nd luciferase assays. The production of specific protein products will be measured by ELISA. The biological activity of these species in the conditioned of specific media of virally-infected vascular cells will be measured in bioassays such as mitogenesis of target smooth muscle cells, and effects on adhesion of monocyte/macrophages and neutrophils to virally-infected endothelial cells. The expression of cellular adhesion molecules on CMV-infected endothelial cells will be evaluated by flow cytometry. The pattern of cytokine activation will be compared with the production of cytokines by alveolar macrophages recovered from bronchoalveolar lavage fluid of bone marrow transplant patients with pneumonitis, with and without CMV infections, as well as to normal alveolar macrophages infected with CMV in vitro to develop an understanding of the interplay between he vasculature and inflammatory cells. These data will help to define the molecular mechanisms of vascular activation induced by viral infection, which may be important in understanding clinical disorders such as CMV pneumonitis in bone marrow transplant recipients.