Intra-amniotic endotoxin increases pulmonary surfactant proteins and induces SP-B processing in fetal sheep

Intra-amniotic (IA) endotoxin induces lung maturation within 6 days in feta l sheep of 125 days gestational age. To determine the early fetal lung resp onse to IA endotoxin, the timing and characteristics of changes in surfacta nt components were evaluated. Fetal sheep were exposed to 20 mg of Escheric hia coli 055:B5 endotoxin by IA injection from 1 to 15 days before preterm delivery at 125 days gestational age. Surfactant protein (SP) A, SP-B, and SP-C mRNAs were maximally induced at 2 days. SP-D mRNA was increased fourfo ld at 1 day and remained at peak levels for up to 7 days. Bronchoalveolar l avage fluid from control animals contained very little SP-B protein, 75% of which was a partially processed intermediate. The alveolar pool of SP-B wa s significantly increased between 4 and 7 days in conjunction with conversi on to the fully processed active airway peptide. All SPs were significantly elevated in the bronchoalveolar lavage fluid by 7 days. IA endotoxin cause d rapid and sustained increases in SP mRNAs that preceded the increase in a lveolar saturated phosphatidylcholine processing of SP-B and improved lung compliance in prematurely delivered lambs.