Alveolar sphingolipids generated in response to TNF-alpha modifies surfactant biophysical activity

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

doi:10.1152/japplphysiol.00184.2002

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Alveolar sphingolipids generated in response to TNF-alpha modifies surfactant biophysical activity

Journal article

Peer reviewed

Alveolar sphingolipids generated in response to TNF-alpha modifies surfactant biophysical activity

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

Journal of applied physiology (1985), Vol.94(1), pp.253-258

01/2003

DOI: 10.1152/japplphysiol.00184.2002

PMID: 12391098

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Abstract

Sphingolipids represent a diverse group of bioactive lipid species that are generated intracellularly in response to tumor necrosis factor-alpha (TNF-alpha) and are implicated as potential mediators of acute lung injury. The purpose of these studies was to determine whether there was an extracellular, TNF-alpha-regulated pool of sphingolipids in the alveolus that modulates the surface tension lowering capacity of pulmonary surfactant. Intratracheal instillation of TNF-alpha in adult rats led to a twofold increase in the amount of surfactant-associated ceramide and tended to decrease levels of sphingomyelin without significantly altering sphingosine or sphinganine content. TNF-alpha induction of alveolar ceramide was associated with nearly an 80% increase in acid sphingomyelinase activity recovered in cell-free alveolar lavage. Ceramide administered in a dose-dependent manner potently antagonized the surface tension lowering effects of natural surfactant in vitro. Intratracheal TNF-alpha and ceramide treatment of rats significantly increased lung permeability, as was evidenced by extravasation of Evans blue dye into alveolar lavage and lung tissue. Thus these studies are the first to demonstrate the existence of a cytokine-regulated alveolar pool of sphingomyelin hydrolysis products that impairs the biophysical properties of the alveolar surfactant film. The results also suggest the presence of a secretory alveolar sphingomylinase that is TNF-alpha responsive and mediates effects of the cytokine on alveolar sphingolipid metabolism.

Surface Tension

Biophysical Phenomena

Capillary Permeability - drug effects

Rats

Male

Pulmonary Surfactants - metabolism

Biophysics

Sphingolipids - physiology

Evans Blue - pharmacokinetics

Rats, Sprague-Dawley

Ceramides - pharmacology

Tumor Necrosis Factor-alpha - pharmacology

Animals

Pulmonary Alveoli - metabolism

Sphingomyelin Phosphodiesterase - metabolism

Coloring Agents - pharmacokinetics

Pulmonary Circulation - drug effects

Details

Title: Subtitle: Alveolar sphingolipids generated in response to TNF-alpha modifies surfactant biophysical activity
Creators: Alan J Ryan - Department of Internal Medicine, The University of Iowa College of Medicine, Iowa City 52242, USA
Diann M McCoy
Stephen E McGowan
Ronald G Salome
Rama K Mallampalli
Resource Type: Journal article
Publication Details: Journal of applied physiology (1985), Vol.94(1), pp.253-258
DOI: 10.1152/japplphysiol.00184.2002
PMID: 12391098
NLM abbreviation: J Appl Physiol (1985)
ISSN: 8750-7587
eISSN: 1522-1601
Publisher: United States
Grant note: HL-68135 / NHLBI NIH HHS HL-55584 / NHLBI NIH HHS HL-71040 / NHLBI NIH HHS
Language: English
Date published: 01/2003
Academic Unit: International Programs; Internal Medicine
Record Identifier: 9983984525502771

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