Eosinophil granular proteins damage bronchial epithelial cells infected with respiratory syncytial virus

Masahiko Kato, Taisei Ishioka, Hirohito Kita, Kunihisa Kozawa, Yasuhide Hayashi, Hirokazu Kimura

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: Respiratory syncytial (RS) virus infection is an important exacerbating factor in acute bronchial asthma. However, the precise mechanisms responsible for viral infection-induced exacerbations of asthma are uncertain. To elucidate the role of eosinophilic inflammation in the pathogenesis of virus-induced asthma, we investigated the effects of eosinophil granule proteins on bronchial epithelial cell infected with RS virus. Methods: Morphological changes and cytopathic effects in human type II pulmonary alveolar epithelial cells (A549) infected with RS virus and/or eosinophil granule proteins such as major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) were observed by microscopy. Apoptosis/necrosis was evaluated by trypan blue exclusion test. We also measured 8 types of phosphorylated proteins in MBP-treated A549 cells infected with RS virus. Results: Although RS virus alone did not affect the cytopathic effects of A549 cells, high concentrations of MBP or a combination of 4 granule proteins resulted in cytopathic effects. MBP or EPO, but not ECP or EDN, induced cytotoxicity and necrosis of the infected A549 cells. Furthermore, MBP induced the phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen-activated protein kinase (MAPK), Jun-N-terminal protein kinase (JNK), and signal transducer and activator of transcription (STAT)3 in the infected cells. Conclusions: These results suggest that eosinophil granule proteins, specifically MBP, damage bronchial epithelial cells infected with RS virus and that the MAPK family are involved in these responses, indicating that eosinophilic inflammation might be associated with the pathophysiology of RS virus-induced acute exacerbations of asthma.

Original languageEnglish (US)
Pages (from-to)11-18
Number of pages8
JournalInternational archives of allergy and immunology
Volume158
Issue numberSUPPL. 1
DOIs
StatePublished - May 2012

Keywords

  • Eosinophil peroxidase
  • Major basic protein
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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