NON-LYTIC EFFECTS OF PHAGOCYTES ON ISOLATED LUNG CELLS

本提案的总体目标是研究 刺激的吞噬细胞及其产物作为非溶解性 分离的肺细胞的反应。 吞噬细胞可能在 肺损伤以及因此它们与分离的肺细胞的相互作用可能 提高我们对临床疾病的理解，如成人呼吸道疾病， 痛苦综合症 先前的研究表明， 表面活性物质分泌是肺泡型损伤的早期指标 II细胞。 使用刺激的中性粒细胞及其 产品还诱导II型细胞表面活性剂分泌的增加。 一 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 嗜中性粒细胞、单核细胞、培养的单核细胞和肺泡巨噬细胞。 的 活性氧作为II型细胞反应诱导物的作用 将使用活性氧物质的清除剂来确定， 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纯化。 的操纵 将进行II型细胞谷胱甘肽周期，以评估 氧化应激对II型细胞对随后的 吞噬细胞暴露。 II型细胞反应的性质和程度 检查受刺激的吞噬细胞。 膜、表面的完整性 受体和合成表面活性剂的能力将被检查。 的 这些吞噬细胞产物导致长期致死的可能性将是 处理。 通过利用这种模型系统的刺激吞噬细胞介导的 答复，希望能够了解可能的 毒性吞噬细胞产物如活性氧参与 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.