title: Imbalance between cysteine proteases and inhibitors in a baboon model of bronchopulmonary dysplasia.
abstract: BACKGROUND
  Bronchopulmonary dysplasia (BPD) continues to be a major morbidity in preterm infants. The lung pathology in BPD is characterized by impaired alveolar and capillary development. An imbalance between proteases and protease inhibitors in association with changes in lung elastic fibers has been implicated in the pathogenesis of BPD.
  
  
  OBJECTIVE
  To investigate the expression and activity levels of papain-like lysosomal cysteine proteases, cathepsins B, H, K, L, S, and their inhibitors, cystatins B and C, in a baboon model of BPD.
  
  
  METHODS
  Real-time reverse transcriptase-polymerase chain reaction, immunohistochemistry, immunoblotting, active site labeling of cysteine proteases, and in situ hybridization were performed.
  
  
  RESULTS
  The steady-state mRNA and protein levels of all cathepsins were significantly increased in the lung tissue of baboons with BPD. In contrast, the steady-state mRNA and protein levels of two major cysteine protease inhibitors, cystatin B and C, were unchanged. Correlating with these alterations, the activity of cysteine proteases in lung tissue homogenates and bronchoalveolar lavage fluid was significantly higher in the BPD group. The levels of cathepsin B, H, and S increased and cathepsin K decreased with advancing gestation. All cathepsins, except for cat K, were immunolocalized to macrophages in BPD. In addition, cathepsin H and cystatin B were colocalized in type 2 alveolar epithelial cells. Cathepsin L was detected in some bronchial epithelial, endothelial, and interstitial cells. Cathepsin K was localized to some perivascular cells by in situ hybridization.
  
  
  CONCLUSIONS
  Cumulatively, these findings demonstrate an imbalance between cysteine proteases and their inhibitors in BPD.
authors.affiliation: Division of Newborn Medicine, Children's Hospital, Boston, MA 02115, USA.
authors.forename: Ozden
authors.initials: O
authors.lastname: Altiok
authors.forename: Ryuji
authors.initials: R
authors.lastname: Yasumatsu
authors.forename: Gulbin
authors.initials: G
authors.lastname: Bingol-Karakoc
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Riese
authors.forename: Mildred T
authors.initials: MT
authors.lastname: Stahlman
authors.forename: William
authors.initials: W
authors.lastname: Dwyer
authors.forename: Richard A
authors.initials: RA
authors.lastname: Pierce
authors.forename: Dieter
authors.initials: D
authors.lastname: Bromme
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Weber
authors.forename: Sule
authors.initials: S
authors.lastname: Cataltepe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000201:enzymology*; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D055313:Cystatin B; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D010215:Papio; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C525030:CST3 protein, human; C524994:CSTB protein, human; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D012333:RNA, Messenger; D055313:Cystatin B; D002403:Cathepsins; D003546:Cysteine Endopeptidases