NON-LYTIC EFFECTS OF PHAGOCYTES ON ISOLATED LUNG CELLS

这项建议的总体目标是研究 刺激吞噬细胞及其产物作为非溶血介质的研究 分离的肺细胞的反应。吞噬细胞可能起到致病作用 肺损伤及其与分离的肺细胞的相互作用可能 加深对成人呼吸道等临床疾病的认识 窘迫综合症。以前的研究已经证明， 肺表面活性物质分泌是肺泡型损害的早期指标 II细胞。利用刺激的中性粒细胞及其功能的初步研究 产品还可以增加II型细胞表面活性物质的分泌。一个 这项建议的具体目的是确定代理人的性质 负责刺激吞噬细胞诱导的II型细胞反应，使用 中性粒细胞、单核细胞、培养单核细胞和肺泡巨噬细胞。这个 活性氧作为II型细胞反应诱导剂的作用 将用活性氧类清除剂测定，改变 吞噬细胞和模型系统。负责的物种将被确定 并从刺激的吞噬细胞上清液中提纯。的操控 将进行II型细胞谷胱甘肽循环，以评估 氧化应激对II型细胞易感性的影响 吞噬细胞暴露。II型细胞反应的性质和程度 将对刺激的吞噬细胞进行检查。膜表面的完整性 将检测受体和合成表面活性物质的能力。这个 这些吞噬细胞产物导致长期致死的可能性将是 地址。通过利用刺激吞噬细胞介导的模型系统 答复，希望能够洞察到可能发生的 有毒的吞噬细胞产物，如活性氧，参与了 肺部疾病。

The overall objective of this proposal is to study the effects of stimulated phagocytes and their products as mediators of non-lytic responses of isolated lung cells. Phagocytes may play a causal role in lung injury and therefore their interaction with isolated lung cells may enhance our understanding of clinical disorders such as adult respiratory distress syndrome. Previous studies have demonstrated that increased surfactant secretion is an early indicator of damage to the alveolar Type II cell. Preliminary studies using stimulated neutrophils and their products also induce an increase in Type II cell surfactant secretion. A specific aim of this proposal is to determine the nature of the agents responsible for stimulated phagocyte induced Type II cell response, using neutrophils, monocytes, cultured monocytes and alveolar macrophages. The role of reactive oxygen species as inducers of the Type II cell responses will be determined using scavengers of reactive oxygen species, altered phagocytes and model systems. The responsible species will be identified and purified from stimulated phagocyte supernatants. Manipulations of the Type II cell glutathione cycle will be performed to assess the effects of oxidant stress on the susceptibility of Type II cells to subsequent phagocyte exposure. The nature and extent of Type II cell responses to stimulated phagocytes will be examined. Integrity of membranes, surface receptors and the ability to synthesize surfactant will be examined. The possibility that these phagocyte products cause long-term lethality will be addressed. By utilizing this model system of stimulated phagocyte-mediated responses, it is hoped that insight will be gained of the possible involvement of toxic phagocyte products such as reactive oxygen species in pulmonary disorders.