Warren J S, Kunkel R G, Johnson K J, Ward P A
Lab Invest. 1987 Sep;57(3):311-20.
IgA immune complex-induced lung injury in the rat is oxygen radical mediated and partially complement-dependent but develops fully after neutrophil depletion. The extent to which monocytes, lung interstitial macrophages, and alveolar macrophages may be involved in the development of lung injury in this model is unclear. To further understand the pathogenesis of IgA lung injury, we have examined the capacity of phagocytic cells isolated from different anatomic compartments of the lung to produce toxic oxygen-derived metabolites. [3H]Thymidine pulse labeling and autoradiography as well as in vivo phagocytosis studies were used to distinguish macrophages isolated from the alveolar and interstitial compartments. Lung interstitial macrophages were characterized ultrastructurally, cytochemically, and functionally. Interstitial macrophages were relatively uniform in size, had blunt pseudopodia, and contained almost no intracytoplasmic lamellar inclusions compared to alveolar macrophages. Similar to monocytes and alveolar macrophages, interstitial macrophages contained nonspecific esterase activity and exhibited the capacity to phagocytize latex and opsonized zymosan particles. Lung interstitial and alveolar macrophages incubated with IgA immune complexes, IgG immune complexes, or phorbol ester (PMA) produced similar amounts of O2-. in a dose-dependent manner. In contrast, peripheral blood neutrophils responded to IgG immune complexes and PMA but not to IgA immune complexes. Monocytes produced a small amount of O2-. in response to PMA but almost no O2-. in response to IgA or IgG immune complexes. These data are consistent with recent in vivo studies which indicate that IgA immune complex lung injury is neutrophil independent. The data provide direct in vitro evidence that lung interstitial and alveolar macrophages produce O2-. following incubation with PMA, IgA, or IgG immune complexes and may therefore contribute to the development of oxygen radical mediated lung injury.
大鼠中IgA免疫复合物诱导的肺损伤是由氧自由基介导的，部分依赖补体，但在中性粒细胞耗竭后仍能充分发展。在该模型中，单核细胞、肺间质巨噬细胞和肺泡巨噬细胞参与肺损伤发展的程度尚不清楚。为了进一步了解IgA肺损伤的发病机制，我们检测了从肺不同解剖部位分离的吞噬细胞产生有毒氧衍生代谢产物的能力。使用[3H]胸腺嘧啶脉冲标记和放射自显影以及体内吞噬研究来区分从肺泡和间质部位分离的巨噬细胞。对肺间质巨噬细胞进行了超微结构、细胞化学和功能特征分析。与肺泡巨噬细胞相比，间质巨噬细胞大小相对均匀，有钝伪足，几乎没有胞质内板层包涵体。与单核细胞和肺泡巨噬细胞相似，间质巨噬细胞含有非特异性酯酶活性，并表现出吞噬乳胶和调理酵母聚糖颗粒的能力。用IgA免疫复合物、IgG免疫复合物或佛波酯（PMA）孵育的肺间质和肺泡巨噬细胞以剂量依赖方式产生相似量的O2-。相比之下，外周血中性粒细胞对IgG免疫复合物和PMA有反应，但对IgA免疫复合物无反应。单核细胞对PMA有少量O2-产生，但对IgA或IgG免疫复合物几乎无O2-产生。这些数据与最近的体内研究一致，表明IgA免疫复合物肺损伤与中性粒细胞无关。这些数据提供了直接的体外证据，表明肺间质和肺泡巨噬细胞在与PMA、IgA或IgG免疫复合物孵育后产生O2-，因此可能有助于氧自由基介导的肺损伤的发展。
