Format

Send to

Choose Destination
Mol Ther. 2018 Aug 1;26(8):2060-2069. doi: 10.1016/j.ymthe.2018.05.017. Epub 2018 Jun 15.

EMAPII Monoclonal Antibody Ameliorates Influenza A Virus-Induced Lung Injury.

Author information

1
Division of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA; VC-CAST Signature Center, Indianapolis, IN, USA; Roudebush Veterans Affairs Medical Center, Indiana University, Indianapolis, IN, USA.
2
VC-CAST Signature Center, Indianapolis, IN, USA; Roudebush Veterans Affairs Medical Center, Indiana University, Indianapolis, IN, USA; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
3
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
4
Division of Pulmonary and Critical Care Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
5
VC-CAST Signature Center, Indianapolis, IN, USA; Roudebush Veterans Affairs Medical Center, Indiana University, Indianapolis, IN, USA; Division of Pulmonary and Critical Care Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
6
Division of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA; VC-CAST Signature Center, Indianapolis, IN, USA; Roudebush Veterans Affairs Medical Center, Indiana University, Indianapolis, IN, USA. Electronic address: nbogatch@iu.edu.

Abstract

Influenza A virus (IAV) remains a major worldwide health threat, especially to high-risk populations, including the young and elderly. There is an unmet clinical need for therapy that will protect the lungs from damage caused by lower respiratory infection. Here, we analyzed the role of EMAPII, a stress- and virus-induced pro-inflammatory and pro-apoptotic factor, in IAV-induced lung injury. First, we demonstrated that IAV induces EMAPII surface translocation, release, and apoptosis in cultured endothelial and epithelial cells. Next, we showed that IAV induces EMAPII surface translocation and release to bronchoalveolar lavage fluid (BALF) in mouse lungs, concomitant with increases in caspase 3 activity. Injection of monoclonal antibody (mAb) against EMAPII attenuated IAV-induced EMAPII levels, weight loss, reduction of blood oxygenation, lung edema, and increase of the pro-inflammatory cytokine TNF alpha. In accordance with the pro-apoptotic properties of EMAPII, levels of caspase 3 activity in BALF were also decreased by mAb treatment. Moreover, we detected EMAPII mAb-induced increase in lung levels of M2-like macrophage markers YM1 and CD206. All together, these data strongly suggest that EMAPII mAb ameliorates IAV-induced lung injury by limiting lung cell apoptosis and shifting the host inflammatory setting toward resolution of inflammation.

KEYWORDS:

EMAPII; IAV; apoptosis; barrier dysfunction; lung injury

PMID:
29910176
PMCID:
PMC6094359
[Available on 2019-08-01]
DOI:
10.1016/j.ymthe.2018.05.017
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center