title: Effects of recombinant Clara cell secretory protein (rhCC10) on inflammatory-related matrix metalloproteinase activity in a preterm lamb model of neonatal respiratory distress.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Interventional laboratory study.
  
  
  METHODS
  An academic medical research facility in the northeastern United States.
  
  
  METHODS
  Sedated, ventilated premature lambs.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Miller
authors.forename: Beth N
authors.initials: BN
authors.lastname: Shashikant
authors.forename: Aprile L
authors.initials: AL
authors.lastname: Pilon
authors.forename: Richard A
authors.initials: RA
authors.lastname: Pierce
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Shaffer
authors.forename: Marla R
authors.initials: MR
authors.lastname: Wolfson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000473:pathology; D008170:Lung Compliance; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011480:Protease Inhibitors / Q000032:analysis; D011650:Pulmonary Alveoli / Q000473:pathology; D011663:Pulmonary Surfactants / Q000627:therapeutic use; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D012756:Sheep; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D016896:Treatment Outcome; D014598:Uteroglobin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D011480:Protease Inhibitors; D011663:Pulmonary Surfactants; C556389:SCGB1A1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D014598:Uteroglobin; D045726:Metalloproteases