Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-α

Nadia Elia, Maxime Tapponnier, Michael A. Matthay, Jürg Hamacher, Jean Claude Pache, Marie Anne Bründler, Martin Totsch, Patrick De Baetselier, Lucie Fransen, Norimasa Fukuda, Denis R. Morel, Rudolf Lucas

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Tumor necrosis factor-α (TNF-α) activates sodium channels in Type II alveolar epithelial cells, an important mechanism for the reported fluid resorption capacity of the cytokine. Both TNF-α 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-α (mTNF-α) was functional in mice that were genetically deficient in both types of mTNF-α receptor, establishing the importance of mTNF-α receptor-independent effects in this species. In addition, we assessed the capacity of an mTNF-α-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-α, 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-α has a potential physiological role in the resolution of alveolar edema in rats and mice.

Original languageEnglish (US)
Pages (from-to)1043-1050
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Issue number9
StatePublished - Nov 1 2003
Externally publishedYes


  • Cytokine
  • Edema
  • Sodium transport

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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