title: Eosinophil granular proteins damage bronchial epithelial cells infected with respiratory syncytial virus.
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.
authors.affiliation: Department of Allergy and Immunology, Gunma Children's Medical Center, Shibukawa, Japan. mkato@gcmc.pref.gunma.jp
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kato
authors.forename: Taisei
authors.initials: T
authors.lastname: Ishioka
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kita
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Kozawa
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kimura
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D047091:Eosinophil Granule Proteins / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000276:immunology
chemical_list: D047091:Eosinophil Granule Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020928:Mitogen-Activated Protein Kinases