Infants with inherited deficiency of pulmonary surfactant protein B (SP-B) develop respiratory failure and die without lung transplantation. We examined content and or synthesis of surfactant components in lung tissue and lavage fluid acquired at transplantation or postmortem from infants with inherited deficiency of SP-B (n=10), other chronic lung diseases (CLD, n=15), and normal infants (n=8). In labeling studies, no immunoprecipitable SP-B was observed in deficient tissue and there was accumulation of a ∼6 kDa form of SP-C. SP-B mRNA was degraded and content was ∼8% of normal in SP-B deficient specimens, however SP-B transcription rates using probes both 5′ and 3′ of the common mutation (121ins2) were comparable in all lungs. The minimal surface tension achieved with lavage surfactant was similarly elevated in both deficient and CLD infants (26-31 mN/m) compared to normals (6 mN/m). Both SP-B deficient and CLD infants had decreased phosphatidylglycerol (PG) content but normal synthetic rates. The overall rate of phospholipid synthesis and PG:PI ratio were elevated in SP-B deficient vs. CLD infants. We conclude that, in infants with SP-B deficiency, the mutated SP-B gene is normally transcribed but produces an unstable mRNA. Absence of SP-B protein blocks processing of SP-C, alters synthesis of phospholipids, and reduces surfactant function.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Jan 1 1999|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)