Deficiency of SP-B reveals protective role of SP-C during oxygen lung injury.
Although the surface properties of surfactant protein (SP)-B and SP-C are similar, the contributions that either protein may make to lung function have not been identified in vivo. Mutations in SP-B cause lethal respiratory failure at birth; however, SP-B null mice are deficient in both SP-B and SP-C. To identify potential contributions of SP-C to lung function in vivo, the following transgenic mice were generated and exposed to 95% O(2) for 3 days: (SP-B(+/+),SP-C(+/+)), (SP-B(+/+), SP-C(-/-)), (SP-B(+/-),SP-C(+/+)), (SP-B(+/-),SP-C(+/-)), and (SP-B(+/-),SP-C(-/-)). Hyperoxia altered pressure-volume curves in mice that were heterozygous for SP-B, and these values were further decreased in (SP-B(+/-),SP-C(-/-)) mice. Likewise, alveolar interleukin (IL)-6 and IL-1 beta were maximally increased by O(2) exposure of (SP-B(+/-),SP-C(-/-)) mice compared with the other genotypes. Lung hysteresivity was lower in the (SP-B(+/-),SP-C(-/-)) mice. Surfactant isolated from (SP-B(+/+),SP-C(-/-)) and (SP-B(+/-),SP-C(-/-)) mice failed to stabilize the surface tension of microbubbles, showing that SP-C plays a role in stabilization or recruitment of phospholipid films at low bubble radius. Genetically decreased levels of SP-B combined with superimposed O(2)-induced injury reveals the distinct contribution of SP-C to pulmonary function in vivo.
Ikegami
Machiko
M
Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio 45229-3039, USA. machiko.ikegami@chmcc.org
Weaver
Timothy E
TE
Conkright
Juliana J
JJ
Sly
Peter D
PD
Ross
Gary F
GF
Whitsett
Jeffrey A
JA
Glasser
Stephan W
SW
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D018496:Hyperoxia / Q000503:physiopathology; D008168:Lung / Q000502:physiology; D008176:Lung Volume Measurements; D051379:Mice; D008822:Mice, Transgenic; D010100:Oxygen; D010713:Phosphatidylcholines / Q000032:analysis; D011014:Pneumonia / Q000139:chemically induced* / Q000503:physiopathology*; D011312:Pressure; D011506:Proteins / Q000032:analysis; D011510:Proteolipids / Q000378:metabolism / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000172:deficiency* / Q000378:metabolism / Q000502:physiology*; D015656:Respiratory Mechanics; D013500:Surface Tension
D016207:Cytokines; D010713:Phosphatidylcholines; D011506:Proteins; D011510:Proteolipids; D011663:Pulmonary Surfactants; D010100:Oxygen