Surfactant protein B corrects oxygen-induced pulmonary dysfunction in heterozygous surfactant protein B-deficient mice

Surfactant protein B (SP-B) is a 79-amino acid hydrophobic surfactant prote in that plays a critical role in postnatal lung function. Homozygous SP-B ( -/-)-deficient mice die of respiratory failure at birth, associated with se vere pulmonary dysfunction and atelectasis. Heterozygous SP-B (+/-)deficien t mice have 50% less SP-B protein, proprotein, and SP-B mRNA compared with control mice and are highly susceptible to oxygen-induced lung injury. In t he current study, we tested whether the susceptibility of SP-B (+/-) mice t o hyperoxia was restored by intratracheal administration of exogenous SP-B. After exposure to 95% oxygen for 3 d, opening pressures were increased and maximal lung volumes were significantly decreased in SP-B (+/-) mice compa red with SP-B (+/+) mice. SP-B (+/-) mice were administered purified bovine SP-B (2%) with DL-alpha dipalmitoyl phosphatidylcholine (DPPC) and 1-palmi toyl-2-oleoyl-sn-glycero-3[phospho-rac-(l-glycerol)] (POPG) phospholipids o r DPPC and POPG phospholipids intratracheally and exposed to 95% oxygen. SP -B-treated SP-B (+/-) mice survived longer in 95% oxygen. Although decrease d lung function in SP-B (+/-) mice exposed to oxygen was not altered by adm inistration of DPPC and POPG, administration of lipids containing 2% purifi ed bovine SP-B restored lung function when assessed after 3 d in oxygen. Ab normalities in pulmonary function in SP-B (+/-) mice after oxygen exposure were associated with increased alveolar capillary leak, which was corrected by administration of SP-B with DPPC and POPG. Likewise, histologic abnorma lities caused by oxygen-induced lung injury were improved by administration of SP-B with DPPC and POPG. Administration of phospholipids with the activ e SP-B peptide was sufficient to restore pulmonary function and prevent alv eolar capillary leak after oxygen exposure, demonstrating the protective ro le of SP-B during oxygen-induced lung injury.