title: Pulmonary matrix metalloproteinase-9 activity in mechanically ventilated children with respiratory syncytial virus.
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.
authors: University of Alabama at Birmingham, Birmingham, AL.
authors: Michele Y F
authors: MY
authors: Kong
authors: John P
authors: JP
authors: Clancy
authors: Ning
authors: N
authors: Peng
authors: Yao
authors: Y
authors: Li
authors: Tomasz J
authors: TJ
authors: Szul
authors: Xin
authors: X
authors: Xu
authors: Robert
authors: R
authors: Oster
authors: Wayne
authors: W
authors: Sullender
authors: Namasivayam
authors: N
authors: Ambalavanan
authors: J Edwin
authors: JE
authors: Blalock
authors: Amit
authors: A
authors: Gaggar
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007440:Intubation; D019272:Leukocyte Elastase / Q000378:metabolism; D008168:Lung / Q000201:enzymology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010100:Oxygen / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D012121:Respiration, Artificial / Q000379:methods*; D018357:Respiratory Syncytial Virus Infections / Q000201:enzymology*; D018113:Respiratory Syncytial Virus, Human; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D009195:Peroxidase; D019272:Leukocyte Elastase; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D010100:Oxygen