This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

Both Prostaglandin E2 and Nitric Oxide Sequentially Mediate the Tumor Necrosis Factor –Induced Inhibition of Surfactant Synthesis by Human Type II Pneumocytes

Elena Vara, PhD; Javier Arias-Díaz, MD, PhD; Cruz Garcia, PhD; Jorge Hernández, MD, PhD; Jose L. Balibrea, MD, PhD

Arch Surg. 1995;130(12):1279-1286.

Abstract
Background
Tumor necrosis factor (TNF-)—induced inhibition of surfactant synthesis seems to participate in the pathogenesis of the adult respiratory distress syndrome.

Objectives
To examine the ability of human type II pneumocytes to produce nitric oxide (NO) in the presence of TNF- and, in addition, to explore the role of this radical in the transduction of the cytokine signal. Design: Multiple organ donors were the source of lung tissue specimens. Type II pneumocytes were isolated by enzymatic digestion, adherence separation of macrophages, and gradient purification. After 24-hour preculture, cells were cultured for 24 hours in the presence or absence of TNF- (100 ng/mL), sodium nitroprusside (100 µmol/L), N-nitro-L-arginine methyl ester (NAME) (1 mmol/L), methylene blue (10 µmol/L), 8-bromo-3',5'-cyclic guanosine monophosphate (8-Br-cGMP) (1 mmol/L), prostaglandin E₂ (PGE₂) (0.1 µmol/L), indomethacin (30 µmol/L), and combinations. The NO release to the medium and cGMP and PGE₂ contents of the cells were measured.

Results
The incorporation of¹⁴C-labeled glucose (D-[U-¹⁴C] glucose) into phosphatidylcholine and phosphatidylglycerol was selectively inhibited either by 8-Br-cGMP or in the presence of TNF-, PGE₂, or nitroprusside, all of which caused an increase in the intracellular levels of cGMP. The inhibitory effect of TNF- was partially reverted by indomethacin, NAME, N-monomethyl arginine, or methylene blue. The inhibitory effect of PGE₂ was partially reverted by NAME, while that of nitroprusside was reverted by methylene blue, but not by indomethacin. Tumor necrosis factor induced an increase in PGE₂ (4.31±0.27 vs 1.65±0.17-pg/µg protein, n=10, P<.01) and cGMP (0.238±0.012 vs 0.109±0.014-pmol/µg protein, n=10, P<.01) cell content and in the NO release to the medium (3.10±0.14 vs 1.19±0.11-nmol/µg protein, n=10, P<.01). The basal NO release to the medium was also increased in the presence of PGE₂. The NAME, which blocked NO generation and cGMP increase, did not affect PGE₂ production in response to TNF-. However, indomethacin, which blocked PGE₂ production, also blunted NO generation and cGMP increase.

Conclusions
The NO generation, secondary to PGE2 production, seems responsible for the TNF-–induced inhibition of phosphatidylcholine synthesis by human type II pneumocytes. Nitric oxide seems to exert this effect through activation of guanylyl cyclase.

(Arch Surg. 1995;130:1279-1286)

Author Affiliations
From the Departments of Biochemistry (Facultad de Medicina) (Drs Vara and García) and Surgery (Hospital San Carlos) (Drs Arias-Díaz, Hernández, and Balibrea), Universidad Complutense, Madrid, Spain.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Inhibition of nitric oxide synthase attenuates NNMU-induced alveolar injury in vivo
Cruz et al.
Am. J. Physiol. Lung Cell. Mol. Physiol. 1997;273:L1167-L1173.
ABSTRACT | FULL TEXT  

Carbon Monoxide Contributes to the Cytokine-Induced Inhibition of Surfactant Synthesis by Human Type II Pneumocytes
Arias-Diaz et al.
Arch Surg 1997;132:1352-1361.
ABSTRACT