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  Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection

Peteranderl, C., Morales-Nebreda, L., Selvakumar, B., Lecuona, E., Vadasz, I., Morty, R. E., et al. (2016). Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection. JOURNAL OF CLINICAL INVESTIGATION, 126(4), 1566-1580. doi:10.1172/JCI83931.

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 Creators:
Peteranderl, Christin, Author
Morales-Nebreda, Luisa, Author
Selvakumar, Balachandar, Author
Lecuona, Emilia, Author
Vadasz, Istvan, Author
Morty, Rory E.1, Author              
Schmoldt, Carole, Author
Bespalowa, Julia, Author
Wolff, Thorsten, Author
Pleschka, Stephan, Author
Mayer, Konstantin, Author
Gattenloehner, Stefan, Author
Fink, Ludger, Author
Lohmeyer, Juergen, Author
Seeger, Werner1, Author              
Sznajder, Jacob I., Author
Mutlu, Goekhan M., Author
Budinger, G. R. Scott, Author
Herold, Susanne, Author
Affiliations:
1Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591698              

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Free keywords: ACTIVATED PROTEIN-KINASE; RESPIRATORY-DISTRESS-SYNDROME; APOPTOSIS-INDUCING LIGAND; ALVEOLAR FLUID CLEARANCE; LIQUID CLEARANCE; VIRUS-INFECTION; IN-VIVO; CYTOKINE RESPONSES; UP-REGULATION; CELLSResearch & Experimental Medicine;
 Abstract: Influenza A viruses (IAV) can cause lung injury and acute respiratory distress syndrome (ARDS), which is characterized by accumulation of excessive fluid (edema) in the alveolar airspaces and leads to hypoxemia and death if not corrected. Clearance of excess edema fluid is driven mostly by the alveolar epithelial Na,K-ATPase and is crucial for survival of patients with ARDS. We therefore investigated whether IAV infection alters Na,K-ATPase expression and function in alveolar epithelial cells (AECs) and the ability of the lung to clear edema. IAV infection reduced Na,K-ATPase in the plasma membrane of human and murine AECs and in distal lung epithelium of infected mice. Moreover, induced Na,K-ATPase improved alveolar fluid clearance (AFC) in IAV-infected mice. We identified a paracrine cell communication network between infected and noninfected AECs and alveolar macrophages that leads to decreased alveolar epithelial Na,K-ATPase function and plasma membrane abundance and inhibition of AFC. We determined that the IAV-induced reduction of Na,K-ATPase is mediated by a host signaling pathway that involves epithelial type I IFN and an IFN-dependent elevation of macrophage TNF-related apoptosis-inducing ligand (TRAIL). Our data reveal that interruption of this cellular crosstalk improves edema resolution, which is of biologic and clinical importance to patients with IAV-induced lung injury.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000373522300042
DOI: 10.1172/JCI83931
 Degree: -

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Title: JOURNAL OF CLINICAL INVESTIGATION
Source Genre: Journal
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Publ. Info: 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA : AMER SOC CLINICAL INVESTIGATION INC
Pages: - Volume / Issue: 126 (4) Sequence Number: - Start / End Page: 1566 - 1580 Identifier: ISSN: 0021-9738