MEDIATORS IN IGA AND IGG LUNG INJURY

我们最近发现，伊加免疫复合物可导致急性损伤， 鼠肺 是否有类似的机制适用于人类间质性肺 疾病是未知的，虽然伊加免疫复合物损伤代表了一种 人类肾小球和血管疾病中的重要问题。 肺 已经发现伊加免疫复合物产生的损伤依赖于 补体，但独立于中性粒细胞，而IgG免疫复合物 伤害需要两种介体系统。 我们将在体外测量 大鼠中性粒细胞和肺泡上皮细胞产生氧自由基 使用各种激动剂，包括IgG和伊加免疫 配合物 将采用的细胞活化的附加参数将 包括酶分泌和花生四烯酸产物产生。 我们将 还探索补体激活产物“增强” 吞噬细胞的O2-。IgG和伊加免疫刺激产生 配合物 这些研究将通过使用高度敏感的流动来辅助。 细胞计数技术。 一系列的体内研究将在 为了确定氧自由基是否参与IgA-免疫复合物 诱发急性肺损伤，如果是，氧气产物是什么类型 涉案 我们将利用最近的研究， 制定了一系列干预措施，旨在确定氧气的作用， 在可能的范围内， 激进分子参与。 还将进行体内研究，以确定 花生四烯酸的产物参与组织损伤。 最后， 从IgG和伊加免疫复合物损伤的肺中回收的吞噬细胞 将在体外检查自发和刺激产生 氧自由基。 这些研究应提供更多信息， 氧自由基在伊加免疫复合物致损伤和肩关节损伤中作用 从而更好地理解伊加免疫复合物 造成组织损伤。

We have recently shown that IgA immune complexes can cause acute injury in rat lung. Whether a similar mechanism pertains in human interstitial lung diseases is not known, although IgA immune complex injury represents a significant problem in human renal glomerular and vascular diseases. Lung injury produced by IgA immune complexes has been found to be dependent on complement but independent of neutrophils, whereas IgG immune complex injury requires both mediator systems. We will measusre in vitro the production of oxygen radicals in both rat neutrophils and alveolar macrophages using a variety of agonists, including IgG and IgA immune complexes. Additional parameters of cell activation to be employed will include enzyme secretion and generation of arachidonate products. We will also explore the ability of complement activation products to "potentiate" phagocytic cells for O2-. production stimulated by IgG and IgA immune complexes. These studies will be aided by the use of highly sensitive flow cytometric techniques. A series of in vivo studies will be carried out in order to determine if oxygen radicals participate in IgA-immune complex induced acute lung injury and, if so, what types of oxygen products are involved. We will take advantage of recent studies in which we have developed a series of interventions designed to define the role of oxygen radicals and to characterize, to the extent possible, the nature of the radical involved. In vivo studies will also be done to determine if products of arachidonic acid are involved in the tissue injury. Finally, phagocytic cells retrieved from IgG and IgA immune complex injured lungs will be examined in vitro for spontaneous as well as stimulated production of oxygen radicals. These studies should provide additional information on the role of oxygen radicals in IgA immune complex induced injury and should lead to a better understanding of the way in which IgA immune complexes bring about tissue injury.