MEDIATORS IN IGA AND IGG LUNG INJURY

我们最近发现，IgA免疫复合体可导致急性损伤 大鼠肺。人类间质肺是否存在类似的机制 疾病尚不清楚，尽管IgA免疫复合体损伤代表着一种 人类肾脏、肾小球和血管疾病的重大问题。肺 已发现由IgA免疫复合体产生的损伤依赖于 补体，但不依赖于中性粒细胞，而免疫复合物 受伤需要两个中介系统。我们将在体外测量 大鼠中性粒细胞和肺泡组织中氧自由基的产生 巨噬细胞使用多种激动剂，包括免疫球蛋白和免疫球蛋白A 复合体。将采用的细胞激活的其他参数将 包括酶分泌和花生四烯酸产物的产生。我们会 同时探索补体激活产物“增强”的能力。 吞噬细胞对O2-的作用。免疫球蛋白和免疫球蛋白A刺激产生 复合体。这些研究将通过使用高度敏感的流动得到帮助。 细胞学技术。一系列体内研究将在 确定氧自由基是否参与免疫球蛋白A免疫复合体 引起的急性肺损伤，如果是的话，有哪些类型的氧气产物 牵涉其中。我们将利用最近的研究，其中我们有 开发了一系列干预措施，旨在定义氧气的作用 并尽可能地刻画其性质 牵涉到激进分子。还将进行体内研究，以确定 花生四烯酸的产物参与了组织损伤。最后， 从受损肺中提取免疫球蛋白和免疫球蛋白A的吞噬细胞 将在体外进行自发和刺激产生的检查 氧自由基组分。这些研究应提供关于以下方面的补充信息 氧自由基在IgA免疫复合体诱导的损伤中的作用及应 有助于更好地了解免疫球蛋白A免疫复合体 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.