Pulmonary surfactant metabolism in infants lacking surfactant protein B.
Infants with inherited deficiency of pulmonary surfactant protein (SP) B develop respiratory failure at birth and die without lung transplantation. We examined aspects of surfactant metabolism in lung tissue and lavage fluid acquired at transplantation or postmortem from ten infants born at term with inherited deficiency of SP-B; comparison groups were infants with other forms of chronic lung disease (CLD) and normal infants. In pulse/chase labeling studies with cultured deficient tissue, no immunoprecipitable SP-B was observed and an approximately 6-kD form of SP-C accumulated that was only transiently present in CLD tissue. SP-B messenger RNA (mRNA) was approximately 8% of normal in deficient specimens, and some intact message was observed after, but not before, explant culture. Transcription rates for SP-B, assessed by nuclear run-on assay using probes for sequences both 5' and 3' of the common nonsense mutation (121ins2), were comparable in all lungs examined. The minimal surface tension achieved with lavage surfactant was similarly elevated in both deficient and CLD infants (26-31 mN/m) compared with normal infants (6 mN/m). Both SP-B-deficient and CLD infants had markedly decreased phosphatidylglycerol content of lavage and tissue compared with normal lung, whereas synthetic rates for phospholipids, including phosphatidylglycerol, were normal. We conclude that the mutated SP-B gene is transcribed normally but produces an unstable mRNA and that absence of SP-B protein blocks processing of SP-C. Chronic infant lung disease, of various etiologies, reduces surfactant function and apparently alters phosphatidylglycerol degradation.
Beers
M F
MF
Department of Medicine, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania, and the Institute for Environmental Medicine, USA.
Hamvas
A
A
Moxley
M A
MA
Gonzales
L W
LW
Guttentag
S H
SH
Solarin
K O
KO
Longmore
W J
WJ
Nogee
L M
LM
Ballard
P L
PL
D000085:Acetates / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D003545:Cysteine / Q000493:pharmacokinetics; D005333:Fetus / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008715:Methionine / Q000493:pharmacokinetics; D010713:Phosphatidylcholines / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism; D011510:Proteolipids / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D014158:Transcription, Genetic / Q000502:physiology; D014316:Tritium
D000085:Acetates; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D014316:Tritium; D008715:Methionine; D003545:Cysteine