Bertram T A, Overby L H, Brody A R, Eling T E
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
Lab Invest. 1989 Oct;61(4):457-66.
Pulmonary intravascular macrophages, as prominent components of the pulmonary mononuclear phagocyte system, could be significant mediators of lung inflammation. We have shown that intravascular and alveolar macrophages metabolize exogenous arachidonic acid to its inflammatory metabolites via the lipoxygenase and cyclooxygenase pathways after exposure to the calcium ionophore A23187. In this study, we compare the metabolism of endogenous arachidonic acid by porcine intravascular and alveolar macrophages after exposure to soluble and particulate stimuli. Since intravascular and alveolar macrophages are exposed to various stimuli in vivo, it is essential to know the range of inflammatory mediators that these cells can generate. Alveolar macrophages attached to plastic and exposed to the various stimuli produced prostaglandin F2 alpha, 12-hydroxyheptade-catrienoic acid (HHT), hydroxyeicosatetraenoic acids (HETE), and leukotriene B4. In contrast, adherent and stimulated intravascular macrophages produced several cyclooxygenase products and lipoxygenase products including 5-HETE, 12-HETE, and leukotriene B4. Both macrophages released large amounts of arachidonic acid upon exposure to each stimulant. Intravascular macrophages that were adherent to plastic or were stimulated with glass, asbestos, or A23187 released significantly (p less than 0.05) more metabolized arachidonic acid than similarly treated alveolar macrophages. The major cyclooxygenase metabolite released by alveolar macrophages was prostaglandin 2 alpha, whereas HHT was the primary metabolite of intravascular macrophages. The major lipoxygenase metabolite released by both macrophage types was 5-HETE, but intravascular macrophages also released substantial amounts of 12-HETE and leukotriene B4. In both macrophage preparations, lipoxygenase products composed most released metabolites. After exposure to iron, asbestos, and A23187 intravascular macrophages released significantly more (p less than 0.05) lipoxygenase metabolites than alveolar macrophages. However, in alveolar macrophages, chrysotile asbestos induced greater activity by the cyclooxygenase pathway than by the lipoxygenase pathway. Both asbestos and iron spheres induced release of arachidonic acid and its metabolites, but the most potent stimulants in both macrophage preparations were A23187, zymosan, and lipopolysaccharide. We conclude that stimulated intravascular macrophages use both cyclooxygenase and lipoxygenase pathways to metabolize endogenous arachidonic acid, that these macrophages are metabolically more active than alveolar macrophages, and that both macrophage types are induced to metabolize arachidonic acid by various particulate and soluble stimuli. Furthermore, we have shown that intravascular macrophages predominantly utilize the lipoxygenase rather than cyclooxygenase pathways to metabolize endogenous arachidonic acid.
肺血管内巨噬细胞作为肺单核吞噬细胞系统的重要组成部分，可能是肺部炎症的重要介质。我们已经表明，血管内和肺泡巨噬细胞在暴露于钙离子载体A23187后，通过脂氧合酶和环氧化酶途径将外源性花生四烯酸代谢为其炎症代谢产物。在本研究中，我们比较了猪血管内和肺泡巨噬细胞在暴露于可溶性和颗粒性刺激后内源性花生四烯酸的代谢情况。由于血管内和肺泡巨噬细胞在体内会受到各种刺激，因此了解这些细胞能够产生的炎症介质范围至关重要。附着于塑料并暴露于各种刺激的肺泡巨噬细胞产生了前列腺素F2α、12-羟基十七碳三烯酸（HHT）、羟基二十碳四烯酸（HETE）和白三烯B4。相比之下，贴壁并受到刺激的血管内巨噬细胞产生了几种环氧化酶产物和脂氧合酶产物，包括5-HETE、12-HETE和白三烯B4。两种巨噬细胞在暴露于每种刺激物后都会释放大量花生四烯酸。附着于塑料或受到玻璃、石棉或A23187刺激的血管内巨噬细胞释放的代谢花生四烯酸明显（p小于0.05）多于同样处理的肺泡巨噬细胞。肺泡巨噬细胞释放的主要环氧化酶代谢产物是前列腺素2α，而HHT是血管内巨噬细胞的主要代谢产物。两种巨噬细胞类型释放的主要脂氧合酶代谢产物都是5-HETE，但血管内巨噬细胞也释放大量的12-HETE和白三烯B4。在两种巨噬细胞制剂中，脂氧合酶产物构成了大多数释放的代谢产物。在暴露于铁、石棉和A23187后，血管内巨噬细胞释放的脂氧合酶代谢产物明显多于肺泡巨噬细胞（p小于0.05）。然而，在肺泡巨噬细胞中，温石棉诱导的环氧化酶途径活性高于脂氧合酶途径。石棉和铁球都诱导了花生四烯酸及其代谢产物的释放，但两种巨噬细胞制剂中最有效的刺激物是A23187、酵母聚糖和脂多糖。我们得出结论，受刺激的血管内巨噬细胞利用环氧化酶和脂氧合酶途径代谢内源性花生四烯酸，这些巨噬细胞在代谢上比肺泡巨噬细胞更活跃，并且两种巨噬细胞类型都被各种颗粒性和可溶性刺激诱导代谢花生四烯酸。此外，我们已经表明，血管内巨噬细胞主要利用脂氧合酶而不是环氧化酶途径代谢内源性花生四烯酸。
