Pulmonary-specific expression of tumor necrosis factor-alpha alters surfactant lipid metabolism

James L Carroll Jr; Diann M McCoy; Stephen E McGowan; Ronald G Salome; Alan J Ryan; Rama K Mallampalli

doi:10.1152/ajplung.00120.2001

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Pulmonary-specific expression of tumor necrosis factor-alpha alters surfactant lipid metabolism

Journal article

Open access

Peer reviewed

Pulmonary-specific expression of tumor necrosis factor-alpha alters surfactant lipid metabolism

James L Carroll Jr, Diann M McCoy, Stephen E McGowan, Ronald G Salome, Alan J Ryan and Rama K Mallampalli

American journal of physiology. Lung cellular and molecular physiology, Vol.282(4), pp.L735-742

04/2002

DOI: 10.1152/ajplung.00120.2001

PMID: 11880299

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Abstract

Tumor necrosis factor (TNF)-alpha is a major cytokine implicated in inducing acute and chronic lung injury, conditions associated with surfactant phosphatidylcholine (PtdCho) deficiency. Acutely, TNF-alpha decreases PtdCho synthesis but stimulates surfactant secretion. To investigate chronic effects of TNF-alpha, we investigated PtdCho metabolism in a murine transgenic model exhibiting lung-specific TNF-alpha overexpression. Compared with controls, TNF-alpha transgenic mice exhibited a discordant pattern of PtdCho metabolism, with a decrease in PtdCho and disaturated PtdCho (DSPtdCho) content in the lung, but increased levels in alveolar lavage. Transgenics had lower activities and increased immunoreactive levels of cytidylyltransferase (CCT), a key PtdCho biosynthetic enzyme. Ceramide, a CCT inhibitor, was elevated, and linoleic acid, a CCT activator, was decreased in transgenics. Radiolabeling studies revealed that alveolar reuptake of DSPtdCho was significantly decreased in transgenic mice. These observations suggest that chronic expression of TNF-alpha results in a complex pattern of PtdCho metabolism where elevated lavage PtdCho may originate from alveolar inflammatory cells, decreased surfactant reuptake, or altered surfactant secretion. Reduced parenchymal PtdCho synthesis appears to be attributed to CCT enzyme that is physiologically inactivated by ceramide or by diminished availability of activating lipids.

Choline Kinase - metabolism

Mice, Inbred C57BL

Tumor Necrosis Factor-alpha - genetics

RNA, Messenger - analysis

Mice, Transgenic

Sphingolipids - metabolism

Tritium

Diacylglycerol Cholinephosphotransferase - metabolism

Blotting, Western

Phosphatidylcholines - pharmacokinetics

Animals

Choline - analogs & derivatives

Choline - pharmacokinetics

Gene Expression - physiology

Lung - metabolism

Mice

Pulmonary Surfactants - pharmacokinetics

Phospholipids - metabolism

Fatty Acids - metabolism

Details

Title: Subtitle: Pulmonary-specific expression of tumor necrosis factor-alpha alters surfactant lipid metabolism
Creators: James L Carroll Jr - University of Iowa
Diann M McCoy
Stephen E McGowan
Ronald G Salome
Alan J Ryan
Rama K Mallampalli
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.282(4), pp.L735-742
DOI: 10.1152/ajplung.00120.2001
PMID: 11880299
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Publisher: American Physiological Society; United States
Grant note: HL-68135 / NHLBI NIH HHS R01 HL-55584 / NHLBI NIH HHS
Language: English
Date published: 04/2002
Academic Unit: International Programs; Internal Medicine
Record Identifier: 9983983647202771

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