Effects of recombinant Clara cell secretory protein (rhCC10) on inflammatory-related matrix metalloproteinase activity in a preterm lamb model of neonatal respiratory distress

• Published in: Pediatric critical care medicine Vol. 8; no. 1; p. 40
• Main Authors: Miller, Thomas L, Shashikant, Beth N, Pilon, Aprile L, Pierce, Richard A, Shaffer, Thomas H, Wolfson, Marla R
• Format: Journal Article
• Language: English
• Published: United States 01.01.2007
• Subjects: Animals; Animals, Newborn; Disease Models, Animal; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - therapeutic use; Humans; Infant, Newborn; Lung - pathology; Lung Compliance; Metalloproteases - antagonists & inhibitors; Metalloproteases - metabolism; Protease Inhibitors - analysis; Pulmonary Alveoli - pathology; Pulmonary Surfactants - therapeutic use; Respiration, Artificial; Respiratory Distress Syndrome, Newborn - drug therapy; Respiratory Distress Syndrome, Newborn - enzymology; Respiratory Distress Syndrome, Newborn - pathology; Respiratory Distress Syndrome, Newborn - therapy; Sheep; Time Factors; Tissue Inhibitor of Metalloproteinase-1 - analysis; Tissue Inhibitor of Metalloproteinase-2 - analysis; Treatment Outcome; Uteroglobin - administration & dosage; Uteroglobin - therapeutic use
• ISSN: 1529-7535; 1947-3893
• DOI: 10.1097/01.pcc.0000253022.10607.61

To test the hypothesis that recombinant Clara cell secretory protein (rhCC10) instillation would foster improved lung function, acute structural preservation, and attenuation of matrix metalloproteinase (MMP) activity in a surfactant-deficient, mechanically ventilated lung. Interventional laboratory study. An academic medical research facility in the northeastern United States. Sedated, ventilated premature lambs. Preterm lambs (n = 18; 126 +/- 3 days gestation) were instrumented, ventilated, and treated with 100 mg/kg exogenous surfactant. Lambs were randomized to receive 0, 0.5, or 5.0 mg/kg rhCC10 (n = 6 per group) and were ventilated for 4 hrs. Posttreatment, lung function and cardiopulmonary stability were monitored for the ventilation period and then animals were killed for in vitro surfactant function analysis, lung histomorphometry, and analysis of MMP-2, -7, and -9 as well as their tissue inhibitors (TIMP)-1 and -2. Ventilation efficiency and pulmonary compliance were improved in the 5.0-mg/kg rhCC10 group by 4 hrs. Lung expansion was variable in the apical regions only. MMP-2 quantity was greater in the apical than the base lung regions of rhCC10-treated groups, and rhCC10 decreased MMP-7 in the base of the lung. These data suggest that improved lung function in the surfactant-treated preterm lamb following intratracheal rhCC10 may be related to the reduction of proteolytic activity of MMP-7.