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

Article Article scientifique Article Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-α eng 2003-07-03 2003-11-01 author Elia Nadia 0000-0003-1787-9288 Division of Anesthesiological Investigations, University Medical Center, Geneva, Switzerland. 87569 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) author Tapponnier Maxime 134603 author Matthay Michael A. author Hamacher Jurg 112559 author Pache Jean-Claude 513830 author Brundler Marie-Anne 526487 author Totsch Martin 513725 author De Baetselier Patrick author Fransen Lucie author Fukuda Norimasa author Morel Denis 22755 author Lucas Rudolf 96458 1043-1050 10.1164/rccm.200206-618oc 12842853 1073-449X https://www.atsjournals.org/doi/10.1164/rccm.200206-618OC 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. Amiloride / pharmacology Animals Biological Transport / physiology Diuretics / pharmacology Female Lung / pathology Male Mice Mice, Inbred C57BL Models, Animal Organ Size Peptide Fragments / metabolism Pulmonary Edema / metabolism Rats Rats, Sprague-Dawley Receptors, Tumor Necrosis Factor / deficiency Receptors, Tumor Necrosis Factor / metabolism Respiratory Mechanics / drug effects Sodium Channels / drug effects Sodium Channels / metabolism Tumor Necrosis Factor-alpha / metabolism Dewey 616.07 Dewey 617 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 137 Département de pathologie et immunologie 21F false American journal of respiratory and critical care medicine 168 9 7ff2dc17-7f3a-42e7-8d47-af25f6c65382 Article (Published version) Public file.pdf 188210 application/pdf 0fc81e751918626080174aedc5937fc90be1ee4e711f0f0e2e85151096fff2ad openAccess Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Functional Identification of the Alveolar Edema Reabsorption Activity of Murine Tumor Necrosis Factor-α	American journal of respiratory and critical care medicine			2003	15	73

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