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Am J Respir Crit Care Med. 2010 Oct 1;182(7):918-28. doi: 10.1164/rccm.200912-1793OC. Epub 2010 Jun 17.

The chitinase-like proteins breast regression protein-39 and YKL-40 regulate hyperoxia-induced acute lung injury.

Author information

1
Department of Pediatrics, and Institute of Allergy, Severance Biomedical Science Institute, BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.

Abstract

RATIONALE:

Prolonged exposure to 100% O(2) causes hyperoxic acute lung injury (HALI), characterized by alveolar epithelial cell injury and death. We previously demonstrated that the murine chitinase-like protein, breast regression protein (BRP)-39 and its human homolog, YKL-40, inhibit cellular apoptosis. However, the regulation and roles of these molecules in hyperoxia have not been addressed.

OBJECTIVES:

We hypothesized that BRP-39 and YKL-40 (also called chitinase-3-like 1) play important roles in the pathogenesis of HALI.

METHODS:

We characterized the regulation of BRP-39 during HALI and the responses induced by hyperoxia in wild-type mice, BRP-39-null (-/-) mice, and BRP-39(-/-) mice in which YKL-40 was overexpressed in respiratory epithelium. We also compared the levels of tracheal aspirate YKL-40 in premature newborns with respiratory failure.

MEASUREMENTS AND MAIN RESULTS:

These studies demonstrate that hyperoxia inhibits BRP-39 in vivo in the murine lung and in vitro in epithelial cells. They also demonstrate that BRP-39(-/-) mice have exaggerated permeability, protein leak, oxidation, inflammatory, chemokine, and epithelial apoptosis responses, and experience premature death in 100% O(2). Lastly, they demonstrate that YKL-40 ameliorates HALI, prolongs survival in 100% O(2), and rescues the exaggerated injury response in BRP-39(-/-) animals. In accord with these findings, the levels of tracheal aspirate YKL-40 were lower in premature infants treated with hyperoxia for respiratory failure who subsequently experienced bronchopulmonary dysplasia or death compared with those that did not experience these complications.

CONCLUSIONS:

These studies demonstrate that hyperoxia inhibits BRP-39/YKL-40, and that BRP-39 and YKL-40 are critical regulators of oxidant injury, inflammation, and epithelial apoptosis in the murine and human lung.

PMID:
20558631
PMCID:
PMC2970863
DOI:
10.1164/rccm.200912-1793OC
[Indexed for MEDLINE]
Free PMC Article

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