Pueringer R J, Hunninghake G W
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Am J Physiol. 1992 Jan;262(1 Pt 1):L78-85. doi: 10.1152/ajplung.1992.262.1.L78.
Lipopolysaccharide (LPS)-stimulated human alveolar macrophages (HAMs) produce large amounts of prostaglandin (PG) E2 for up to 72 h. The mechanism of this enhanced and prolonged metabolism of arachidonic acid to PGE2 is unknown. To determine whether LPS-stimulated HAM PGE2 production is due in part to an increase in the new synthesis of the first committed enzyme, PGH synthase, we measured PGE2 formation, PGH synthase activity, and newly synthesized PGH synthase at 2, 6, and 24 h after LPS-stimulation. PGE2, measured by radioimmunoassay, was not increased at 2 h but was increased at 6 and 24 h after stimulating HAMs with LPS. Unstimulated HAMs did not produce PGE2. Likewise, the activity of PGH synthase extracted from HAMs was not increased at 2 h but was increased at 6 and 24 h after LPS stimulation. Cycloheximide and actinomycin D markedly inhibited PGE2 production in LPS-stimulated HAMs. Newly synthesized PGH synthase measured by immunoprecipitating 35S-labeled PGH synthase was not detected at 2 h but was detected at 6 and 24 h after stimulation. The parallel increases in PGE2 production, PGH synthase activity, and newly synthesized PGH synthase coupled with the dependence of PGE2 on the ability of the alveolar macrophage to synthesize protein suggest that LPS-stimulated HAM PGE2 production is in part regulated by the de novo synthesis of PGH synthase.
脂多糖（LPS）刺激的人肺泡巨噬细胞（HAMs）可在长达72小时内产生大量前列腺素（PG）E2。花生四烯酸向PGE2这种增强且延长的代谢机制尚不清楚。为了确定LPS刺激的HAMs产生PGE2是否部分归因于首个关键酶PGH合酶新合成的增加，我们在LPS刺激后的2小时、6小时和24小时测量了PGE2的生成、PGH合酶活性以及新合成的PGH合酶。通过放射免疫测定法测得的PGE2在LPS刺激HAMs后的2小时未增加，但在6小时和24小时增加。未受刺激的HAMs不产生PGE2。同样，从HAMs中提取的PGH合酶活性在LPS刺激后的2小时未增加，但在6小时和24小时增加。放线菌酮和放线菌素D显著抑制LPS刺激的HAMs中PGE2的产生。通过免疫沉淀35S标记的PGH合酶测得的新合成PGH合酶在刺激后的2小时未检测到，但在6小时和24小时检测到。PGE2生成、PGH合酶活性和新合成的PGH合酶的平行增加，以及PGE2对肺泡巨噬细胞合成蛋白质能力的依赖性表明，LPS刺激的HAMs产生PGE2部分受PGH合酶从头合成的调节。
