Lamellar body formation precedes pulmonary surfactant apoprotein expression during embryonic mouse lung development in vivo and in vitro

Slavkin, Harold C.; Johnson, R.B.; Oliver, Peter; Bringas, Pablo; Don-Wheeler, Grace; Mayo, Mark L.; Whitsett, JA

doi:10.1111/j.1432-0436.1989.tb00751.x

Cited by 23 publications

(15 citation statements)

References 74 publications

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“…In the most severely affected animal, B5, there were no recognizable mature, distal respiratory epithelial cells present of any cell type. Instead, the residual respiratory epithelium consisted of cuboidal cells resembling immature type II cells with patches of glycogen that frequently contained forming lamellar membranes similar to those described in the day-12 to -14 fetal mouse (19,20). Although small organelles resembling immature lamellar bodies were seen both intra-and extracellularly in this animal, no extracellular tubular myelin was seen.…”

Section: Resultssupporting

confidence: 61%

Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice.

Korfhagen

Glasser

Wert

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

104

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Pulmonary surfactant is produced in late gestation by developing type II epithelial cells lining the alveolar epithelium of the lung. Lack of surfactant at birth is associated with respiratory distress syndrome in premature infants. Surfactant protein C (SP-C) is a highly hydrophobic peptide isolated from pulmonary tissue that enhances the biophysical activity of surfactant phospholipids. Like surfactant phospholipid, SP-C is produced by epithelial cells in the distal respiratory epithelium, and its expression increases during the latter part of gestation. A chimeric gene containing 3.6 kilobases of the promoter and 5'-flanking sequences of the human SP-C gene was used to express diphtheria toxin A. The SP-C-diphtheria toxin A fusion gene was injected into fertilized mouse eggs to produce transgenic mice. Affected mice developed respiratory failure in the immediate postnatal period. Morphologic analysis of lungs from affected pups showed variable but severe cellular injury confined to pulmonary tissues. Ultrastructural changes consistent with cell death and injury were prominent in the distal respiratory epithelium. Proximal components of the tracheobronchial tree were not severely affected. Transgenic animals were of normal size at birth, and structural abnormalities were not detected in nonpulmonary tissues. Lung-specific diphtheria toxin A expression controlled by the human SP-C gene injured type II epithelial cells and caused extensive necrosis of the distal respiratory epithelium. The absence of type I epithelial cells in the most severely affected transgenic animals supports the concept that developing type II cells serve as precursors to type I epithelial cells.

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Section: Resultssupporting

confidence: 61%

Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice.

Korfhagen

Glasser

Wert

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

104

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“…Thus, the developmental appearance of SP-A and lecithin could be readily distinguished. Slavkin et al (34) observed the appearance of lamellar bodies before detection of SP-A expression, suggesting that the surfactant apoproteins are regulated independently of the surfactant phospholipids and are not necessary for early lamellar body formation. Differences in timing of expression of SP-A and SP-B support the concept that the proteins are also independently regulated.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of Surfactant Proteins A and B in Human Amniotic Fluid as Indices of Fetal Lung Maturity

et al. 1991

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ABSTRACT. Surfactant proteins A and B (SP-A and SP-B) were measured in human amniotic fluid by ELISA and correlated with lecithin to sphingomyelin ratio (L/S), phosphatidylglycerol (PG), and perinatal outcome. Amniotic fluid SP-A, SP-B, and L/S increased with advancing gestation. SP-A was detected at 19 wk gestation and increased dramatically in the 3rd trimester of pregnancy. SP-B was first detectable at 31 wk gestation and increased significantly to term. SP-A was a more specific predictor of nonrespiratory distress syndrome (RDS) than L/S or SP-B; however, the sensitivity of SP-A in predicting RDS was less than L/S < 2.0 (26.3 versus 82.3%, respectively). In 209 pregnancies assessed within 48 h of delivery, the sensitivity of SP-B in predicting RDS (nondetectable SP-B) was comparable to the L/S, however, SP-B = 0 was frequently observed in mature infants, limiting its specificity for prediction of RDS. The greatest sensitivity and specificity were achieved with the measurement of L/S < 3). SP-B is an M, = 8700 hydrophobic polypeptide that imparts biophysical properties of rapid spreading and adsorption to surfactant phospholipids (for review, see Ref. 4). The surfactant phospholipids and associated proteins are developmentally regulated, appearing in the fetal rat lung between 18 and 19 d of gestation and increasing until birth (5-7). Lung fluid, including surfactant, contributes to the composition of amniotic fluid. Amniotic fluid content of saturated phosphatidylcholine (lecithin), PG, and phosphatidylinositol parallel the expression of these phospholipids in the fetal lung and have been used to estimate fetal lung maturity (8-13). Human amniotic fluid content of SP-A also increases with advancing gestation and is predictive of fetal lung maturity and development of .RDS continues to be a major cause of morbidity and mortality in premature infants. Accurate estimates of fetal lung maturity are required for optimal pennatal-neonatal management of highrisk pregnancies. The L/S and the presence of P C are routinely used to predict the development of RDS (9, 1 1, 14). The accuracy of the combined L/S and P C tests is approximately 90-95%. A high incidence of false-negative results occurs particularly with the L/S, such that fetal lung immaturity is predicted in many cases where neonatal pulmonary function is mature. In the present study, concentrations of SP-A and SP-B in human amniotic fluid were determined by capture ELISA. The predictive value of the amniotic fluid concentration of SP-A and SP-B for neonatal pulmonary disease was compared with that of the L/S and PC. MATERIALS AND METHODSAmniotic fluid samples (n = 473) were obtained from 408 high-risk pregnancies at the University of Cincinnati between

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“…Lungs from adult SP-A(+/-), (-/-), and (+/+) mice were immunostained for SP-A, proSP-B, and proSP-C using guinea pig anti-rat polyclonal SP-A and rabbit polyclonal proSP-B and proSP-C antiserum as described (15)(16)(17) were prepared by inflation fixation and embedded in paraffin before sectioning. For Western blot analysis of lung homogenates, mice were euthanized under protocols approved by the Institutional Animal Use and Care Committee.…”

Section: Methodsmentioning

confidence: 99%

Altered surfactant function and structure in SP-A gene targeted mice.

Korfhagen

Bruno

Ross

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

383

302

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Lamellar body formation precedes pulmonary surfactant apoprotein expression during embryonic mouse lung development in vivo and in vitro

Cited by 23 publications

References 74 publications

Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice.

Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice.

Ontogeny of Surfactant Proteins A and B in Human Amniotic Fluid as Indices of Fetal Lung Maturity

Altered surfactant function and structure in SP-A gene targeted mice.

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