Vara E, Arias-Díaz J, García C, Hernández J, Balibrea J L
Department of Biochemistry (Facultad de Medicina), Universidad Complutense, Madrid, Spain.
Am J Physiol. 1996 Sep;271(3 Pt 1):L359-65. doi: 10.1152/ajplung.1996.271.3.L359.
Tumor necrosis factor-alpha (TNF-alpha)-induced inhibition of surfactant synthesis participates in the pathogenesis of the acute respiratory distress syndrome. We examined the ability of human type II pneumocytes to produce nitric oxide (NO) in the presence of TNF-alpha as well as the role of NO and prostaglandin (PG) E2 in the transduction of the cytokine signal. Multiple organ donors were used as a source of lung tissue. After 24-h preculture, type II pneumocytes were cultured for 18 h in the presence or absence of additives. The D-[U-14C] glucose incorporation into phosphatidylcholine (PC) was selectively inhibited by TNF-alpha, PGE2, sodium nitroprusside (SNP), or 8-bromoguanosine 3',5'-cyclic monophosphate. The effect of TNF-alpha was attenuated by indomethacin, N omega-nitro-L-arginine methyl ester (NAME), or methylene blue (MB). The effect of PGE2 was attenuated by NAME, while that of SNP was reversed by MB but not by indomethacin. TNF-alpha induced an increase in PGE2 and guanosine 3',5'-cyclic monophosphate cell content and in the NO release to the medium. NAME did not affect PGE2 production, while indomethacin blunted NO generation. Our results suggest that NO generation, secondary to PGE2 production, is responsible for the TNF-alpha-induced inhibition of PC synthesis by human type II pneumocytes.
肿瘤坏死因子-α（TNF-α）诱导的表面活性剂合成抑制参与急性呼吸窘迫综合征的发病机制。我们研究了人II型肺细胞在TNF-α存在下产生一氧化氮（NO）的能力，以及NO和前列腺素（PG）E2在细胞因子信号转导中的作用。多器官供体作为肺组织来源。经过24小时预培养后，II型肺细胞在有或无添加剂的情况下培养18小时。TNF-α、PGE2、硝普钠（SNP）或8-溴鸟苷3',5'-环一磷酸可选择性抑制D-[U-14C]葡萄糖掺入磷脂酰胆碱（PC）。吲哚美辛、Nω-硝基-L-精氨酸甲酯（NAME）或亚甲蓝（MB）可减弱TNF-α的作用。NAME可减弱PGE2的作用，而MB可逆转SNP的作用，但吲哚美辛不能。TNF-α可诱导PGE2和鸟苷3',5'-环一磷酸细胞含量增加以及NO释放到培养基中。NAME不影响PGE2的产生，而吲哚美辛可减弱NO的生成。我们的结果表明，继发于PGE2产生的NO生成是TNF-α诱导人II型肺细胞PC合成抑制的原因。
