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

[tetano]

J Clin Invest. 2016 Mar 21. pii: 83931. doi: 10.1172/JCI83931. [Epub ahead of print]
[h=1]Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection.[/h] Peteranderl C, Morales-Nebreda L, Selvakumar B, Lecuona E, Vad?sz I, Morty RE, Schmoldt C, Bespalowa J, Wolff T, Pleschka S, Mayer K, Gattenloehner S, Fink L, Lohmeyer J, Seeger W, Sznajder JI, Mutlu GM, Budinger GR, Herold S.
[h=3]Abstract[/h] 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.


PMID: 26999599 [PubMed - as supplied by publisher]

 

[tetano]

J Clin Invest. 2016 Mar 21. pii: 86802. doi: 10.1172/JCI86802. [Epub ahead of print]
[h=1]Influenza leaves a TRAIL to pulmonary edema.[/h] Brauer R, Chen P.
[h=3]Abstract[/h] Influenza infection can cause acute respiratory distress syndrome (ARDS), leading to poor disease outcome with high mortality. One of the driving features in the pathogenesis of ARDS is the accumulation of fluid in the alveoli, which causes severe pulmonary edema and impaired oxygen uptake. In this issue of the JCI, Peteranderl and colleagues define a paracrine communication between macrophages and type II alveolar epithelial cells during influenza infection where IFNα induces macrophage secretion of TRAIL that causes endocytosis of Na,K-ATPase by the alveolar epithelium. This reduction of Na,K-ATPase expression decreases alveolar fluid clearance, which in turn leads to pulmonary edema. Inhibition of the TRAIL signaling pathway has been shown to improve lung injury after influenza infection, and future studies will be needed to determine if blocking this pathway is a viable option in the treatment of ARDS.


PMID: 26999598 [PubMed - as supplied by publisher]