Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-{alpha}

Tumor necrosis factor-alpha (TNF-alpha) activates sodium channels in Type II alveolar epithelial cells, an important mechanism for the reported fluid resorption capacity of the cytokine. Both TNF-alpha receptor-dependent and -independent effects were proposed for this activity in vitro, the latter m...

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Published in:American journal of respiratory and critical care medicine 2003-11, Vol.168 (9), p.1043
Main Authors: Elia, Nadia, Tapponnier, Maxime, Matthay, Michael A, Hamacher, Jurg, Pache, Jean-Claude, Brundler, Marie-Anne, Totsch, Martin, De Baetselier, Patrick, Fransen, Lucie, Fukuda, Norimasa, Morel, Denis R, Lucas, Rudolf
Format: Article
Language:English
Subjects:
Cytokines
Edema
Ischemia
Lectins
Lungs
Peptides
Pneumonia
Sodium
Tumor necrosis factor-TNF
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Summary:Tumor necrosis factor-alpha (TNF-alpha) activates sodium channels in Type II alveolar epithelial cells, an important mechanism for the reported fluid resorption capacity of the cytokine. Both TNF-alpha receptor-dependent and -independent effects were proposed for this activity in vitro, the latter mechanism mediated by the lectin-like domain of the molecule. In this study, the relative contribution of the receptor-dependent versus receptor-independent activities was investigated in an in situ mouse lung model and an ex vivo rat lung model. Fluid resorption due to murine TNF-alpha (mTNF-alpha) was functional in mice that were genetically deficient in both types of mTNF-alpha receptor, establishing the importance of mTNF-alpha receptor-independent effects in this species. In addition, we assessed the capacity of an mTNF-alpha-derived peptide (mLtip), which activates sodium transport by a receptor-independent mechanism, to reduce lung water content in an isolated, ventilated, autologous blood-perfused rat lung model. The results show that in this model, mLtip, in contrast to mTNF-alpha, produced a progressive recovery of dynamic lung compliance and airway resistance after alveolar flooding. There was also a significant reduction in lung water. These results indicate that the receptor-independent lectin-like domain of mTNF-alpha has a potential physiological role in the resolution of alveolar edema in rats and mice.
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.200206-618OC