EMAPII Monoclonal Antibody Ameliorates Influenza A Virus-Induced Lung Injury

Hongyan Lu, Sarvesh Chelvanambi, Christophe Poirier, Jacob Saliba, Keith L. March, Matthias Clauss, Natalia Bogatcheva

Research output: Contribution to journalArticle

2 Citations (Scopus)

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. Infection with influenza A virus is followed by the membrane translocation and release of pro-apoptotic and pro-inflammatory mediator EMAPII. Here, Lu and colleagues show that EMAPII neutralization with monoclonal antibody attenuates epithelial apoptosis and barrier dysfunction in vitro and mitigates influenza A virus-induced lung injury in vivo.

Original languageEnglish (US)
JournalMolecular Therapy
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Influenza A virus
Lung Injury
Monoclonal Antibodies
Lung
Bronchoalveolar Lavage Fluid
Apoptosis
Caspase 3
Weight Loss
Respiratory Tract Infections
Cultured Cells
Edema
Endothelial Cells
Tumor Necrosis Factor-alpha
Epithelial Cells
Macrophages
Cytokines
Viruses
Inflammation
Injections
Membranes

Keywords

  • apoptosis
  • barrier dysfunction
  • EMAPII
  • IAV
  • lung injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

EMAPII Monoclonal Antibody Ameliorates Influenza A Virus-Induced Lung Injury. / Lu, Hongyan; Chelvanambi, Sarvesh; Poirier, Christophe; Saliba, Jacob; March, Keith L.; Clauss, Matthias; Bogatcheva, Natalia.

In: Molecular Therapy, 01.01.2018.

Research output: Contribution to journalArticle

Lu, Hongyan ; Chelvanambi, Sarvesh ; Poirier, Christophe ; Saliba, Jacob ; March, Keith L. ; Clauss, Matthias ; Bogatcheva, Natalia. / EMAPII Monoclonal Antibody Ameliorates Influenza A Virus-Induced Lung Injury. In: Molecular Therapy. 2018.
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