Surfactant protein B in human fetal lung: developmental and glucocorticoid regulation.
Pulmonary surfactant protein B (SP-B) enhances phospholipid film formation in vitro and is essential for normal surfactant function in vivo. We examined human fetal lung before and during explant culture for content and cellular localization of SP-B mRNA and protein. SP-B mRNA was low in preculture specimens (18-20 wk) but hybridization signal increased over epithelial cells during culture and was enhanced by dexamethasone treatment (10 nM). SP-B immunofluorescence was very low in preculture specimens, increased during culture, and was uniformly intense in epithelial cells of dexamethasone-treated tissue. With a newly developed immunoassay, SP-B protein was undetectable in preculture lung (< 2% of adult), appeared during culture (26% of adult), and was further increased approximately 3-fold by dexamethasone treatment (86% of adult); lung tissue of two newborn infants contained 7-9-fold more SP-B than is found in the adult. Using Western blot with enhanced chemiluminescence, mature SP-B was undetectable in 16-wk specimens but was present in 19-24-wk preculture tissue at 0.2-2.9% of the adult level. By comparison, SP-B mRNA content is 14 and 50% of adult level in 19- and 24-wk lung tissue, respectively; levels increase 3-fold during culture and a further 3-fold with dexamethasone. Based on these observed differences between mRNA and protein content, we conclude that basal SP-B gene expression in epithelial cells of human fetal lung is regulated primarily at the level of translation or protein stability, whereas glucocorticoids act transcriptionally. We speculate that SP-B protein accumulates only as type II cells differentiate and acquire lamellar bodies for processing and storage of SP-B.
Beers
M F
MF
Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, USA.
Shuman
H
H
Liley
H G
HG
Floros
J
J
Gonzales
L W
LW
Yue
N
N
Ballard
P L
PL
D000328:Adult; D015153:Blotting, Western; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D008168:Lung / Q000196:embryology / Q000378:metabolism* / Q000601:surgery; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D013194:Staining and Labeling
D005938:Glucocorticoids; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D003907:Dexamethasone