Introduction/Purpose Matrix metalloproteinases (MMP)-8 and -9 have been implicated in acute lung injury (ALI) in adults. Little is known about their role in pediatric ALI, particularly as the disease progresses from the acute, exudative phase to the chronic fibroproliferative phase.
Methods Lower airway secretions from 26 pediatric patients (age < 18 years) intubated for respiratory failure were collected and analyzed. Samples from those who developed ALI lasting greater than 10 days (n = 12) were compared with their early-phase samples (days 0-10). Samples from 14 healthy pediatric subjects intubated for elective surgery were used as controls. Samples were probed for MMP expression and activity using immunoblotting and ELISA-based quantitative analysis.
Results Notable differences were seen in MMP-8 and MMP-9 expression profiles and regulation. Pooled samples from the first 10 days of ALI demonstrated up-regulation of MMP-8 (ALI 67 ± 24 ng/mg; 3.7-fold increase over control), and MMP-9 (ALI 599 ± 117 ng/mg; 2.6-fold increase over control), with MMP-9 activity exceeding MMP-8 (p < .0002). Analyses of pooled ALI samples (days 11-15) demonstrated decreasing MMP-9 activity (139 ng/mg ± 53 ng/mg, p < .002) compared with earlier pooled samples (days 0-10) and retention of endogenous negative regulation. In contrast, MMP-8 demonstrated increasing activity with disease progression (112 ± 41 ng/mg; 63% increase). In a subset of patients, MMP-8 activity became primarily constitutive, suggesting loss of negative regulation with disease progression. MMP-8 isoforms identified in later samples were predominantly lower-molecular-weight species (40-60 kDa), suggesting an important role of MMP-8 release from mesenchymal cells.
Conclusion Our data suggest that in pediatric ALI, MMP-8 activity increases whereas MMP-9 activity decreases with disease progression. Determining whether this shifting MMP profile can be used as a marker for protracted respiratory failure or the development of the fibroproliferative stage in the pediatric population warrants further examination.
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