tetano
Editor, Senior Moderator
J Virol. 2015 Dec 4. pii: JVI.02599-15. [Epub ahead of print]
[h=1]Influenza infection induces platelet-endothelial adhesion which contributes to lung injury.[/h] Sugiyama M[SUP]1[/SUP], Gamage A[SUP]2[/SUP], Zyla R[SUP]3[/SUP], Armstrong SM[SUP]2[/SUP], Advani S[SUP]3[/SUP], Advani A[SUP]3[/SUP], Wang C[SUP]3[/SUP], Lee WL[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Lung injury after influenza is characterized by increased permeability of the lung microvasculature culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both lab and clinical strains of influenza increased adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells suggesting a paracrine effect. Influenza infection caused upregulation of von Willebrand factor and ICAM-1 but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited both by RGDS peptide and by a blocking antibody to platelet integrin α[SUB]5[/SUB]β[SUB]1[/SUB], implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition were also observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsaclicylic acid significantly improved survival, a finding confirmed using a second anti-platelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. Inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.
[h=4]IMPORTANCE:[/h] There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza. We have recently shown that the virus can infect human lung endothelial cells, but the functional consequences of this infection are unknown. Here we show that this infection causes platelets to adhere to the lung endothelium. Importantly, blocking platelets using two distinct anti-platelet drugs improved survival in a mouse model of severe influenza infection. Thus, platelet inhibition may constitute a novel therapeutic strategy to improve the host response to severe infections with influenza.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26637453 [PubMed - as supplied by publisher]
[h=1]Influenza infection induces platelet-endothelial adhesion which contributes to lung injury.[/h] Sugiyama M[SUP]1[/SUP], Gamage A[SUP]2[/SUP], Zyla R[SUP]3[/SUP], Armstrong SM[SUP]2[/SUP], Advani S[SUP]3[/SUP], Advani A[SUP]3[/SUP], Wang C[SUP]3[/SUP], Lee WL[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Lung injury after influenza is characterized by increased permeability of the lung microvasculature culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both lab and clinical strains of influenza increased adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells suggesting a paracrine effect. Influenza infection caused upregulation of von Willebrand factor and ICAM-1 but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited both by RGDS peptide and by a blocking antibody to platelet integrin α[SUB]5[/SUB]β[SUB]1[/SUB], implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition were also observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsaclicylic acid significantly improved survival, a finding confirmed using a second anti-platelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. Inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.
[h=4]IMPORTANCE:[/h] There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza. We have recently shown that the virus can infect human lung endothelial cells, but the functional consequences of this infection are unknown. Here we show that this infection causes platelets to adhere to the lung endothelium. Importantly, blocking platelets using two distinct anti-platelet drugs improved survival in a mouse model of severe influenza infection. Thus, platelet inhibition may constitute a novel therapeutic strategy to improve the host response to severe infections with influenza.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26637453 [PubMed - as supplied by publisher]