Surfactant protein-B-deficient mice are susceptible to hyperoxic lung injury

Keisuke Tokieda, Harriet S. Iwamoto, Cindy Bachurski, Susan E. Wert, William M. Hull, Kazushige Ikeda, Jeffrey A. Whitsett

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77 Citations (Scopus)

Abstract

Surfactant protein-B (SP-B) is a small, hydrophobic pcptide that plays a critical role in pulmonary function and surfactant homeostasis. To determine whether SP-B protects mice from oxygen-induced injury, heterozygous SP-B+/- gene-targeted mice and wild-type SP-B+/+ littermates were exposed to hyperoxia (95% oxygen for 3 d) or room air. Although specific lung compliance in room air in SP-B+/- mice was slightly reduced as compared with that in SP-B+/+ mice, it was reduced more markedly during hyperoxia (46% versus 25% decrease, respectively). The larger decrease in lung compliance in SP-B+/- mice was associated with increased severity of pulmonary edema, hemorrhage and inflammation, lung permeability and protein leakage into the alveolar space. Hyperoxia increased SP-B messenger RNA (mRNA) and total protein concentrations by 2-fold in SP-B+/+ and SP-B+/- mice, but decreased the abundance of SP-B protein in lavage fluid relative to total protein only in SP-B+/- mice. Hyperoxia increased SP-B expression, but apparently not enough to maintain SP-B function and lung compliance in the presence of increased protein leakage in SP-B+/- mice. Increased alveolar-capillary leakage and relative deficiency of SP-B may therefore contribute to oxygen-induced pulmonary dysfunction in SP-B+/- mice. These data support the concept that SP-B plays an important protective role in the lung.

Original languageEnglish
Pages (from-to)463-472
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume21
Issue number4
DOIs
Publication statusPublished - 1999 Jan 1

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Tokieda, K., Iwamoto, H. S., Bachurski, C., Wert, S. E., Hull, W. M., Ikeda, K., & Whitsett, J. A. (1999). Surfactant protein-B-deficient mice are susceptible to hyperoxic lung injury. American journal of respiratory cell and molecular biology, 21(4), 463-472. https://doi.org/10.1165/ajrcmb.21.4.3436