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 journalArticle

56 Citations (Scopus)

Abstract

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
Volume168
Issue number9
DOIs
StatePublished - Nov 1 2003
Externally publishedYes

Fingerprint

Edema
Tumor Necrosis Factor-alpha
Tumor Necrosis Factor Receptors
Lung
Mitogen Receptors
Alveolar Epithelial Cells
Lung Compliance
Airway Resistance
Water
Sodium Channels
Lectins
Sodium
Cytokines
Peptides

Keywords

  • Cytokine
  • Edema
  • Sodium transport

ASJC Scopus subject areas

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

Cite this

Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-α. / Elia, Nadia; Tapponnier, Maxime; Matthay, Michael A.; Hamacher, Jürg; Pache, Jean Claude; Bründler, Marie Anne; Totsch, Martin; De Baetselier, Patrick; Fransen, Lucie; Fukuda, Norimasa; Morel, Denis R.; Lucas, Rudolf.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 168, No. 9, 01.11.2003, p. 1043-1050.

Research output: Contribution to journalArticle

Elia, N, Tapponnier, M, Matthay, MA, Hamacher, J, Pache, JC, Bründler, MA, Totsch, M, De Baetselier, P, Fransen, L, Fukuda, N, Morel, DR & Lucas, R 2003, 'Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-α', American Journal of Respiratory and Critical Care Medicine, vol. 168, no. 9, pp. 1043-1050. https://doi.org/10.1164/rccm.200206-618OC
Elia, Nadia ; Tapponnier, Maxime ; Matthay, Michael A. ; Hamacher, Jürg ; Pache, Jean Claude ; Bründler, Marie Anne ; Totsch, Martin ; De Baetselier, Patrick ; Fransen, Lucie ; Fukuda, Norimasa ; Morel, Denis R. ; Lucas, Rudolf. / Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-α. In: American Journal of Respiratory and Critical Care Medicine. 2003 ; Vol. 168, No. 9. pp. 1043-1050.
@article{e06dbfb374324abea38f44e9258f6e70,
title = "Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-α",
abstract = "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.",
keywords = "Cytokine, Edema, Sodium transport",
author = "Nadia Elia and Maxime Tapponnier and Matthay, {Michael A.} and J{\"u}rg Hamacher and Pache, {Jean Claude} and Br{\"u}ndler, {Marie Anne} and Martin Totsch and {De Baetselier}, Patrick and Lucie Fransen and Norimasa Fukuda and Morel, {Denis R.} and Rudolf Lucas",
year = "2003",
month = "11",
day = "1",
doi = "10.1164/rccm.200206-618OC",
language = "English (US)",
volume = "168",
pages = "1043--1050",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "9",

}

TY - JOUR

T1 - Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-α

AU - Elia, Nadia

AU - Tapponnier, Maxime

AU - Matthay, Michael A.

AU - Hamacher, Jürg

AU - Pache, Jean Claude

AU - Bründler, Marie Anne

AU - Totsch, Martin

AU - De Baetselier, Patrick

AU - Fransen, Lucie

AU - Fukuda, Norimasa

AU - Morel, Denis R.

AU - Lucas, Rudolf

PY - 2003/11/1

Y1 - 2003/11/1

N2 - 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.

AB - 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.

KW - Cytokine

KW - Edema

KW - Sodium transport

UR - http://www.scopus.com/inward/record.url?scp=10744223644&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744223644&partnerID=8YFLogxK

U2 - 10.1164/rccm.200206-618OC

DO - 10.1164/rccm.200206-618OC

M3 - Article

VL - 168

SP - 1043

EP - 1050

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 9

ER -