Bertram T A, Overby L H, Danilowicz R, Eling T E, Brody A R
Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Am Rev Respir Dis. 1988 Oct;138(4):936-44. doi: 10.1164/ajrccm/138.4.936.
Pulmonary intravascular macrophages are a recently identified component of the pulmonary mononuclear phagocyte system. It has been shown that alveolar macrophages are capable of metabolizing arachidonic acid (AA) to its biologically active inflammatory metabolites via the lipoxygenase and cyclooxygenase pathways. In this study, we have compared the ability of swine intravascular macrophages and alveolar macrophages to metabolize AA in vitro. Alveolar macrophages attached to a plastic substrate produced at least five identified AA metabolites including prostaglandin (PG)F2 alpha, hydroxyheptadecatrienoic acid (HHT), 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, and 15-HETE. In contrast, adherent intravascular macrophages produced eight identified metabolites including thromboxane (TX)B2, PGF2 alpha, PGD2, PGE2, HHT, 5-HETE, 12-HETE, and 15-HETE. The major lipoxygenase metabolite produced by both macrophage types was 5-HETE. The major cyclooxygenase metabolite produced by alveolar macrophages was PGF2 alpha, whereas the major metabolite produced by intravascular macrophages was HHT. Both macrophage populations treated with calcium ionophore (A23187) exhibited increased production of PGs, TXB2, leukotriene (LT)B4, 5-HETE, 12-HETE, and 15-HETE, but the most striking increase occurred in metabolism through the lipoxygenase pathway. The major lipoxygenase metabolite generated by ionophore-stimulated macrophages was 5-HETE, and in intravascular macrophages 12-HETE was also produced. Preincubation of macrophages with indomethacin and nordihydroguaiaretic acid attenuated the yield of cyclooxygenase metabolites and lipoxygenase metabolites, respectively. Studies of leukotriene formation demonstrated that both macrophage types produce LTC4 and LTB4 from the leukotriene precursor LTA4. Thus, we show that the pulmonary intravascular macrophage is capable of metabolizing AA and LTA4 to their inflammatory and vasoactive metabolites by the cyclooxygenase and lipoxygenase pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
肺血管内巨噬细胞是肺单核吞噬细胞系统中最近才被确认的一个组成部分。业已表明，肺泡巨噬细胞能够通过脂氧合酶和环氧化酶途径将花生四烯酸（AA）代谢为具有生物活性的炎性代谢产物。在本研究中，我们比较了猪血管内巨噬细胞和肺泡巨噬细胞在体外代谢AA的能力。附着于塑料基质上的肺泡巨噬细胞产生了至少五种已确认的AA代谢产物，包括前列腺素（PG）F2α、羟十七碳三烯酸（HHT）、5-羟基二十碳四烯酸（5-HETE）、12-HETE和15-HETE。相比之下，贴壁的血管内巨噬细胞产生了八种已确认的代谢产物，包括血栓素（TX）B2、PGF2α、PGD2、PGE2、HHT、5-HETE、12-HETE和15-HETE。两种巨噬细胞类型产生的主要脂氧合酶代谢产物均为5-HETE。肺泡巨噬细胞产生的主要环氧化酶代谢产物是PGF2α，而血管内巨噬细胞产生的主要代谢产物是HHT。用钙离子载体（A23187）处理的两种巨噬细胞群体均表现出PGs、TXB2、白三烯（LT）B4、5-HETE、12-HETE和15-HETE的生成增加，但最显著的增加发生在通过脂氧合酶途径的代谢中。离子载体刺激的巨噬细胞产生的主要脂氧合酶代谢产物是5-HETE，并且在血管内巨噬细胞中还产生了12-HETE。用吲哚美辛和去甲二氢愈创木酸对巨噬细胞进行预孵育分别减弱了环氧化酶代谢产物和脂氧合酶代谢产物的产量。白三烯形成的研究表明，两种巨噬细胞类型均从白三烯前体LTA4产生LTC4和LTB4。因此，我们表明肺血管内巨噬细胞能够通过环氧化酶和脂氧合酶途径将AA和LTA4代谢为它们的炎性和血管活性代谢产物。（摘要截短至250字）
