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Am J Respir Crit Care Med. 2007 Oct 15;176(8):778-85. Epub 2007 Aug 2.

Cathepsin S deficiency confers protection from neonatal hyperoxia-induced lung injury.

Author information

  • 1Division of Newborn Medicine, Brigham and Women's Hospital, Thorn 1019, 75 Francis Street, Boston, MA 02115, USA.

Abstract

RATIONALE:

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that adversely affects long-term pulmonary function as well as neurodevelopmental outcomes of preterm infants. Elastolytic proteases have been implicated in the pathogenesis of BPD. Cathepsin S (cat S) is a cysteine protease with potent elastolytic activity. Increased levels and activity of cat S have been detected in a baboon model of BPD.

OBJECTIVES:

To investigate whether deficiency of cat S alters the course of hyperoxia-induced neonatal lung injury in mice.

METHODS:

Newborn wild-type and cat S-deficient mice were exposed to 80% oxygen for 14 days. Histologic and morphometric analysis were performed and bronchoalveolar lavage protein and cells were analyzed. Lung elastin was assessed by real-time polymerase chain reaction, in situ hybridization, desmosine analysis, and Hart's stain. Distribution of myofibroblasts was analyzed by immunofluorescence. Hydroxyproline content of lung tissues was measured.

MEASUREMENTS AND MAIN RESULTS:

Hyperoxia-exposed cat S-deficient mice were protected from growth restriction and had improved alveolarization, decreased septal wall thickness, lower number of macrophages, and lower protein concentration in bronchoalveolar lavage fluid. alpha-Smooth muscle actin-expressing myofibroblasts accounted for at least some of the increased interstitial cellularity in hyperoxia-exposed mouse lungs and were significantly less in cat S-deficient lungs. Lung hydroxyproline content was increased in hyperoxia-exposed wild-type, but not in cat S-deficient lungs. Desmosine content was significantly reduced in both genotypes with hyperoxia.

CONCLUSIONS:

Cathepsin S deficiency improves alveolarization, and attenuates macrophage influx and fibroproliferative changes in hyperoxia-induced neonatal mouse lung injury.

PMID:
17673697
[PubMed - indexed for MEDLINE]
PMCID:
PMC2020827
Free PMC Article

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