Surfactant protein-B-deficient mice are susceptible to hyperoxic lung injury.
Surfactant protein-B (SP-B) is a small, hydrophobic peptide 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.
Tokieda
K
K
Division of Neonatology and Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Iwamoto
H S
HS
Bachurski
C
C
Wert
S E
SE
Hull
W M
WM
Ikeda
K
K
Whitsett
J A
JA
D000818:Animals; D005260:Female; D006579:Heterozygote; D018496:Hyperoxia / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008170:Lung Compliance; D055370:Lung Injury; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability; D011498:Protein Precursors / Q000378:metabolism; D011510:Proteolipids / Q000235:genetics* / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D011498:Protein Precursors; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger