Deficiency of SP-B reveals protective role of SP-C during oxygen lung injury

Abstract

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% O2 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-1β were maximally increased by O2 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 O2-induced injury reveals the distinct contribution of SP-C to pulmonary function in vivo.