Related Experiment Videos
Implications for matrix metalloproteinases as modulators of pediatric lung disease
Margaret K Winkler1, Jane K Foldes, Robert C Bunn
1Department of Pediatrics, University of Alabama at Birmingham, 35233, USA. Mwinkler@peds.uab.edu
Insights
Matrix metalloproteinases (MMPs) are elevated in children with respiratory failure. These enzymes may play a role in pediatric lung damage and disease.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Pediatric Respiratory Research
Background:
- Matrix metalloproteinases (MMPs) are crucial for lung development but can also mediate lung damage.
- Limited knowledge exists regarding MMP production in children's lungs and their role in lung injury.
Purpose of the Study:
- To investigate MMP activity and expression in pediatric endotracheal aspirates.
- To compare MMP levels in healthy children versus those with respiratory failure.
Main Methods:
- Analysis of endotracheal aspirates from children (<19 years).
- Assay for gelatinase activity and inhibitor profiling.
- Quantification of MMP-7, MMP-8, and MMP-9 concentrations and activities.
Main Results:
- Gelatinase activity was 5-6 times higher in children with respiratory failure.
- MMP-7, MMP-8, and MMP-9 concentrations and activities were significantly elevated in respiratory failure.
- MMP-7, MMP-8, and MMP-9 levels showed significant correlations in children with lung disease.
Conclusions:
- Specific MMPs are present in diseased pediatric lungs.
- Elevated MMPs may contribute to the pathogenesis of pediatric respiratory failure.
Abstract:
Matrix metalloproteinases (MMPs) are a large family (>20) of cation-dependent proteinases believed to be important modulators of normal human lung development and potentially harmful mediators of lung damage. Little is known about MMP production and secretion by the lung during childhood or how alterations in MMP levels may be involved in lung damage. We examined endotracheal aspirates from children (<19 years) without lung disease for the presence of MMP activity. Only gelatinase activity was detectable, and inhibitor profiles suggest they represented one or more MMPs. Comparison of gelatinase activity, MMP expression, and MMP activity in children without pulmonary disease with children who required mechanical ventilation for respiratory failure show: 1) gelatinase activity was approximately five- to sixfold higher in respiratory failure; 2) MMP-7, MMP-8, and MMP-9 concentrations and MMP-8 and MMP-9 activities were markedly elevated in respiratory failure; and 3) MMP-7, MMP-8, and MMP-9 levels were significantly correlated in children with lung disease. These studies provide compelling evidence that specific MMPs are present in the diseased lung and may participate in the pathogenesis of pediatric respiratory failure.