Pulmonary matrix metalloproteinase-9 activity in mechanically ventilated children with respiratory syncytial virus.

Academic Article

Abstract

  • Respiratory syncytial virus (RSV) infection is a potent stimulus for airway epithelial expression of matrix metalloproteinase (MMP)-9. MMP-9 activity in vivo is a predictor of disease severity in children with RSV-induced respiratory failure. Human airway epithelial cells were infected with RSV A2 strain and analysed for MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 (a natural inhibitor of MMP-9) release. In addition, endotracheal samples from children with RSV-RF and controls (non-RSV pneumonia and nonlung disease controls) were analysed for MMP-9, TIMP-1, human neutrophil elastase and myeloperoxidase activity. RSV infection of airway epithelia was sufficient to rapidly induce MMP-9 transcription and protein release. Pulmonary MMP-9 activity peaked at 48 h in infants with RSV-induced respiratory failure. In the RSV group, MMP-9 activity and MMP-9/TIMP-1 ratio imbalance predicted higher oxygen requirement and worse paediatric risk of mortality scores. The highest levels of human neutrophil elastase and myeloperoxidase activity were measured in the RSV cohort; however, unlike MMP-9, these neutrophil markers failed to predict disease severity. These results support the hypothesis that RSV is a potent stimulus for MMP-9 expression and release from human airway epithelium, and that MMP-9 is an important biomarker of disease severity in mechanically ventilated children with RSV lung infection.
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    Keywords

  • Biomarkers, Cells, Cultured, Child, Child, Preschool, Female, Gene Expression Regulation, Enzymologic, Humans, Infant, Infant, Newborn, Intubation, Leukocyte Elastase, Lung, Male, Matrix Metalloproteinase 9, Oxygen, Peroxidase, Respiration, Artificial, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Human, Tissue Inhibitor of Metalloproteinase-1
  • Digital Object Identifier (doi)

    Author List

  • Kong MYF; Clancy JP; Peng N; Li Y; Szul TJ; Xu X; Oster R; Sullender W; Ambalavanan N; Blalock JE
  • Start Page

  • 1086
  • End Page

  • 1096
  • Volume

  • 43
  • Issue

  • 4