INTERACTIONS BETWEEN ALVEOLAR TYPE II CELL AND CYTOKINES IN THE LUNG INJURY

目的：肺泡II型细胞的增殖是多种原因引起的肺泡损伤修复的关键，本研究旨在探讨肺泡II型细胞与炎症细胞因子和/或介质在肺损伤中的相互作用。结果：1)肺泡II型细胞和炎性细胞因子。IL-1β以剂量和时间依赖的方式增强大鼠肺泡II型细胞DNA中的胸腺嘧啶核苷掺入。抗IL-1β抗体或IL-1受体拮抗剂可部分抑制IL-1β对胸腺嘧啶核苷掺入的影响。它们的结合完全抑制了IL-1β的作用。在没有IL-1β的情况下，联合用药可将[~(3 H)]胸腺嘧啶核苷掺入抑制到低于对照组的水平。这些结果表明，外源性IL-1β刺激肺泡II型细胞的DNA合成，并内源性产生IL-1β，提示内源性I-…更多的L-1β可能参与了肺泡型细胞的基础DNA合成。肺表面活性物质与肺损伤我们研究了外源性表面活性物质(表面活性物质TA)与中性粒细胞功能之间的潜在相互作用。第0天气管内注射博莱霉素(5 mg/kg)诱导大鼠中性粒细胞肺泡炎。第1天用表面活性物质TA(5 mg/100g体重和10 mg/100g体重)替代部分动物。第2天取肺泡细胞，用博莱霉素和表面活性物质处理的肺泡细胞中性粒细胞的数量没有变化，但这些细胞产生的超氧自由基明显低于对照组(未用表面活性物质TA)。体外实验表明，表面活性剂TA能抑制中性粒细胞的黏附和超氧化物的产生。经表面活性物质-TA处理的中性粒细胞具有野味核，并表达Fas抗原，这是凋亡细胞的特征。这些结果提示，外源性表面活性物质TA可能不仅在改善表面活性物质功能方面发挥重要作用，而且可能通过促进细胞凋亡来阻止中性粒细胞的进一步激活。3)肺泡液清除机制。肺泡钠通过肺泡II型细胞顶膜上的钠通道进入，并被基底膜上的Na，K-1和ATP酶泵出。水主要通过跨细胞水孔蛋白途径跟随钠离子的运动。K^&lt；ATP&gt；通道开放剂可增加肺泡液清除量，从而影响K的转运和肺泡上皮细胞的净向量液运动。较少

PURPOSE : Proliferation of alveolar type II cells is critical for restoration of the integrity of alveolar injuries caused by a number of different etiologies, In this project, we aimed to investigate interactions between alveolar type II cell and inflammatory cytokines and or mediators in the lung injury. RESULTS : 1) Alveolar type II cells and inflammatory cytokines. IL-1 beta enhanced a [^3H] Thymidine incorporation dose- and time-dependently into DNA in rat alveolar type II cells. Anti-IL-1 beta antibody or IL-1 receptor antagonist partially inhibited thee effects of IL-1 beta on [^3H] Thymidine incorporation. Their combination completely inhibited the effects of IL-1 beta. In the absence of IL-1 beta, the combination inhibited the [^3H] Thymidine incorporation to a level under that in the control. These results dumonstrate that exogenous IL-1 beta stimulates DNA synthesis in alveolar type II cells and the cells also produce IL-1 beta endogenously, and suggest that the endogenous I … More L-1 beta may mediate basal DNA synthesis of alveolar type cells. Lung surfactant and lung injury. We invastigated potential interactions between exogenous surfactant (Surfactant TA) and neutrophil functions. Neutrophil alveolitis was induced in hamster lungs by the intratracheal administration of bleomycin (5mg/kg) on Day 0. Some of the animals were followed by replacement with Surfactant TA (5 and 10mg/1OOg BW) on Day 1. Alveolar cells were harvested by lung lavage on Day 2. The numbers of the neutrophils obtained from the lungs treated with bleomycin and Surfactant were unchanged, but the superoxido production from these cells was significantly decreased when compared with control animals (no Surfactant TA). From the in vitro experiments Surfactant TA was shown to inhibit adherence and superoxide production of human neutrophils. Surfactant-TA-treated neutrophils were demonstrated to have picnotic nuclei and to express Fas antigens, which were characteristic of apoptotic cells. These results suggest that exogenous Surfactant TA may play an important role not only in improving surfactant functions but in preventing neutrophils from further activation, probably through enhancing apoptosis. 3) Mechanisms of alveolar fluid clearance. Alveolar sodium enters through sodium channels on the apical membrane of alveolar type II cells and is pumped out by a Na, K-^<ATP> ase on the basolateral membrane. Water follows sodium movement primarily through transcellular aquaporin pathways. Alveolar fluid clearance increased by K^<ATP> channel opener which could effect K transport and net vectorial fluid movement across the human alveolar epithelium. Less