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

目的：肺泡II型细胞的增殖对于由多种不同病因引起的肺泡损伤的完整性恢复至关重要。在本项目中，我们旨在研究肺泡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型细胞与炎症因子。IL-1 β增强大鼠肺泡II型细胞胸苷苷与DNA结合的剂量和时间依赖性。抗IL-1抗体或IL-1受体拮抗剂部分抑制IL-1 β对[^3H]胸苷结合的三种作用。它们的结合完全抑制了IL-1 β的作用。在缺乏IL-1 β的情况下，该组合抑制[^3H]胸苷的掺入，使其达到低于对照组的水平。这些结果表明，外源性IL-1 β刺激肺泡型细胞的DNA合成，细胞也内源性产生IL-1 β，提示内源性IL-1 β可能介导肺泡型细胞的基础DNA合成。肺表面活性剂与肺损伤。我们研究了外源性表面活性剂（表面活性剂TA）与中性粒细胞功能之间的潜在相互作用。第0天气管内给予博来霉素（5mg/kg）诱导仓鼠肺中性粒细胞肺泡炎。部分动物在第1天用表面活性剂TA（5和10mg/ 10g BW）替代。第2天通过肺灌洗收集肺泡细胞。博来霉素和表面活性剂处理后的肺中性粒细胞数量没有变化，但与对照组（不含表面活性剂TA）相比，这些细胞的超氧化物产生明显减少。体外实验表明，表面活性剂TA能抑制人中性粒细胞的粘附和超氧化物的产生。表面活性剂- ta处理的中性粒细胞被证明具有小核和表达Fas抗原，这是凋亡细胞的特征。这些结果表明，外源性表面活性剂TA不仅可以改善表面活性剂的功能，而且可能通过促进细胞凋亡来阻止中性粒细胞的进一步活化。肺泡液清除的机制。肺泡钠通过肺泡II型细胞顶膜上的钠通道进入，并由基底侧膜上的Na， K-^<ATP>酶泵出。水跟随钠的运动主要通过跨细胞水通道蛋白途径。K^<ATP>通道开启器增加了肺泡液清除率，这可能影响K转运和净载体液体在人肺泡上皮中的运动。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