Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Vadász, I; Morty, RE; Olschewski, A; Königshoff, M; Kohstall, MG; Ghofrani, HA; Grimminger, F; Seeger, W.
Thrombin impairs alveolar fluid clearance by promoting endocytosis of Na+,K+-ATPase.
AMER J RESPIR CELL MOLEC BIOL 2005 33: 343-354.
Doi: 10.1165/rcmb.2004-0407OC
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Olschewski Andrea
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Coagulation is an emerging area of interest in the pathogenesis and treatment of acute lung injury. Concentrations of the edemagenic coagulation protease thrombin are elevated in plasma and lavage fluids from afflicted patients. We explored the impact of thrombin on the formation and resolution of alveolar edema. Intravascularly applied thrombin inhibited active transepithelial 22Na transport in intact rabbit lungs, suppressing alveolar fluid clearance. Epithelial permeability was unaffected, whereas endothelial permeability was increased. In A549 human lung epithelial cells and in mouse primary alveolar type II cells, thrombin blocked ouabain-sensitive Na+,K+-ATPase-mediated 86Rb+ uptake, without altering amiloride-sensitive sodium currents. Furthermore, thrombin downregulated cell-surface expression of Na+,K+-ATPase, but not ENaC alpha and beta subunits. The endocytosis inhibitor phalloidin oleate blocked all thrombin-induced effects on sodium transport activity. Similarly, diphenyleneiodonium chloride, an inhibitor of reactive oxygen radical production, as well as a protein kinase C-zeta inhibitor, prevented these thrombin-induced effects. Thus, thrombin signaling via reactive oxygen species and protein kinase C-zeta promotes Na+,K+-ATPase endocytosis, resulting in loss of function. We propose here a dual role for thrombin in mediating disturbances to fluid balance in the lung: thrombin concomitantly provokes edema formation by increasing endothelial permeability, and inhibits alveolar edema resolution by blocking Na+,K+-ATPase function.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Line -
- Cell Membrane Permeability -
- Endocytosis - physiology
- Enzyme Inhibitors - metabolism
- Extracellular Fluid - metabolism
- Humans - metabolism
- Male - metabolism
- Mice - metabolism
- Na(+)-K(+)-Exchanging ATPase - metabolism
- Ouabain - metabolism
- Patch-Clamp Techniques - metabolism
- Protein Kinase C - metabolism
- Pulmonary Alveoli - metabolism
- Rabbits - metabolism
- Reactive Oxygen Species - metabolism
- Research Support, Non-U.S. Gov't - metabolism
- Signal Transduction - physiology
- Sodium Channels - metabolism
- Thrombin - metabolism
- Find related publications in this database (Keywords)
- acute respiratory distress syndrome
- coagulation
- permeability
- protein kinase C-xi
- reactive oxygen species