Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression profiles in tracheal aspirates do not adequately reflect tracheal or lung tissue profiles in neonatal respiratory distress: Observations from an animal model

Objective: Matrix metalloproteinase (MMP)/tissue inhibitor of matrix metalloproteinase (TIMP) expression in tracheal aspirates (TA) is commonly assayed to represent the protein profile in the lung. This study tests the hypothesis that the profile of MMPs 2, 7, and 9 and the profile of TIMPs 1 and 2 will be different in TA, tracheal tissue, and lung tissue in neonatal respiratory distress. Design: Interventional laboratory study. Setting: An academic medical research facility in northeastern United States. Subjects: Oleic acid-injured, spontaneously breathing newborn piglets. Interventions: Ten piglets (3-4 days old, 2.4 ± 0.4 kg) were instrumented, injured by intravenous administration of oleic acid, and supported on continuous positive airway pressure of 2-5 cm H₂O, with or without exogenous surfactant, depending on physiologic requirements. Measurement and Main Results: After 6 hrs, TA, trachea, and lung were obtained for MMP/TIMP analysis by substrate zymography/reverse zymography. TA contained less active (p < .01) and more latent (p < .05) MMP-2 than trachea and lung, and the active/latent ratio was less in TA than in both tissues (p < .01). TA and trachea contained more total (p < .05) and active (p < .01) MMP-9 than did the lung; TA contained more active MMP-9 than trachea (p < .01). MMP-7 was greater in all forms relative to total protein (p < .01) from both tissues compared with TA. Trachea contained more latent MMP-7 than lung (p < .01). TIMP-1 was different across protein sources (p < .01) where TA < trachea < lung. The active MMP-2/TIMP-2 ratio was lower in TA than in lung (p < .01); the MMP-9/TIMP-1 ratio had a significant trend (p < .01) where TA > trachea > lung. Conclusions: The MMP/TIMP profiles in TA do not adequately represent the profiles in either trachea or lung. Thus, MMP/TIMP profiles from TA are limited and should be interpreted for trends rather than actual tissue levels.