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Intermedin Stabilized Endothelial Barrier Function And Attenuated Ventilator-Induced Lung Injury In Mice
- Source :
- A61. LUNG ENDOTHELIUM FUNCTIONS: THE BARRIER AND BEYOND.
- Publication Year :
- 2011
- Publisher :
- American Thoracic Society, 2011.
-
Abstract
- Rationale: Even protective ventilation may aggravate or induce lung failure, particularly in preinjured lungs. Thus, new adjuvant pharmacologic strategies are needed to attenuate ventilator induced lung injury (VILI). Intermedin/Adrenomedullin II (IMD) stabilized pulmonary endothelial barrier function in vitro. We hypothesized that IMD may attenuate VILI-associated lung permeability in vivo. Methods: Human umbilical vein endothelial cell (HUVEC) monolayers were incubated with IMD and transendothelial electrical resistance was measured to quantify endothelial barrier function. Expression and localisation of endogenous pulmonary IMD, and its receptor complexes composed of CRLR und RAMP1-3 were analyzed by qPCR and immunoflourescence in unventilated mouse lungs and in lungs ventilated for 6h. In untreated and IMD treated mice, lung permeability and pulmonary leukocyte recruitment was assessed after mechanical ventilation. Results: IMD stabilized endothelial barrier function in HUVECs. Mechanical ventilation reduced the expression of RAMP 3, but not of IMD, CRLR, and RAMP1 and 2. Mechanical ventilation induced lung permeability, which was ameliorated by IMD treatment. IMD did not reduce VILI associated pulmonary leukocyte recruitment. Conclusion: We showed for the first time that IMD had endothelial barrier stabilizing properties in vivo. IMD may possibly provide a new approach to attenuate ventilator-induced lung injury.
Details
- Database :
- OpenAIRE
- Journal :
- A61. LUNG ENDOTHELIUM FUNCTIONS: THE BARRIER AND BEYOND
- Accession number :
- edsair.doi...........365635684665c94de42ac87413819d1f