Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-α
| Autor: | Maxime Tapponnier, Jean-Claude Pache, Marie Anne Bründler, Michael A. Matthay, Patrick De Baetselier, Norimasa Fukuda, Denis R. Morel, Jürg Hamacher, Nadia Elia, Martin Tötsch, Rudolf Lucas, Lucie Fransen |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty medicine.medical_treatment Pulmonary Edema Critical Care and Intensive Care Medicine Receptors Tumor Necrosis Factor Sodium Channels Amiloride Rats Sprague-Dawley Mice Animals Medicine Diuretics Receptor Lung Tumor Necrosis Factor-alpha business.industry Reabsorption Biological Transport Organ Size Peptide Fragments Rats Resorption Cell biology Mice Inbred C57BL medicine.anatomical_structure Cytokine Models Animal Respiratory Mechanics Female Tumor necrosis factor alpha Pulmonary alveolus business Ex vivo |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 168:1043-1050 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.200206-618oc |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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