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PubMed1984

Sex-related differences in cellular composition and surfactant synthesis of developing fetal rat lungs.

Differences in pulmonary surfactant production by male and female fetuses in late gestation have been suggested, but the precise relationship of these findings to the changing cellular populations in the lung as development progresses has not been investigated previously. Using sexed rat littermates from Day 18 to 22 of gestation, we correlated the epithelial, endothelial, and interstitial cell composition of the lung with disaturated phosphatidylcholine (DSPC) content and with the incidence of lamellar bodies in epithelial cells and air sacs. At Days 19 and 20, female rat lungs had a higher content of DSPC than did the lungs of male littermates. At Days 20 and 21, more cuboidal epithelial cells of female fetuses contained lamellar bodies, and more air sacs in the female lung contained lipid material, than was observed in males. Sex-related differences in lung structure were seen even earlier. From Day 18 to Day 20, there was a greater proportion of epithelial cells in female lungs than in the lungs of male littermates; just before birth the cellular composition was similar. The results show that differentiation of epithelium with lamellar body formation and DSPC production occurs sooner in females. However, it is suggested that a sex-related difference in lung development occurs much earlier in the female at the onset of a phase of epithelial growth.

Animals↗
PubMed1995

Early protein oxidation in the neonatal lung is related to development of chronic lung disease.

Free radical-mediated oxidation of proteins may impair their function and cause cellular damage. We studied pulmonary protein oxidation and its association with the development of chronic lung disease in 61 newborn infants (mean gestational age 31.1 +/- 4.0, range 24-41 weeks) requiring intensive care with oxygen therapy. Protein oxidation was quantified as protein carbonylation in tracheal aspirates recovered daily during the first week of life. Mean carbonyl concentration was 3.5 +/- 1.6 mumol/mg protein. Negative correlations existed between protein carbonylation during days 2-4 and gestational age (day 2: r = -0.37, p = 0.01; day 3: r = -0.48, p = 0.001; and day 4: r = -0.33, p = 0.03). Patients who developed bronchopulmonary dysplasia showed significantly higher protein carbonylation on days 1-6 (all p < 0.05). In multiple regression analysis explaining bronchopulmonary dysplasia, using gestational age, inspired oxygen on days 1-3 and protein carbonylation on day 3 as independent variables, only protein carbonylation remained significant. We conclude that immaturity is the most important factor explaining free radical-mediated pulmonary protein oxidation in newborn infants and that oxidation of proteins is related to the development of chronic lung disease.

Bronchopulmonary Dysplasia↗
PubMed2004

Development of lung function in early life: influence of birth weight in infants of nonsmokers.

This study aimed to compare lung growth and development during the first year of life in healthy term infants of low or appropriate birth weight for gestation. Paired measurements of forced expiratory volume in 0.4 second, FVC, and forced expiratory flow when 75% of FVC has been exhaled were obtained, using the raised volume technique, at about 7 weeks and 9 months of age in 80 infants (32 low and 48 appropriate birth weight for gestation) of white, nonsmoking mothers. Forced flows and volumes increased with growth. Longitudinal trends in results were compared between the two groups, using random effects modeling and adjusted for potential confounding factors. After adjustment for sex, age, and length, forced expiratory volume was significantly reduced by an average (95% confidence interval) of 9% (2 to 16%) in low birth weight compared with appropriate birth weight for gestation infants throughout the first year of life, with a similar trend in forced expiratory flow (8% [-2 to 17%]) and FVC (4% [-3 to 11%]). These findings suggest that lung function is reduced in low birth weight for gestation infants born to nonsmoking white mothers and that this is independent of somatic growth during infancy.

Birth Weight↗
PubMed1997

Fetal pulmonary development: the role of respiratory movements.

The lung develops before birth as a collapsible, liquid-filled, organ. Throughout the later stages of gestation the fetal lungs are maintained at a level of expansion that is considerably greater than the level achieved as a result of passive equilibration between lung recoil and the chest wall. Fetal breathing movements (FBM) are a feature of normal fetal life and, as such, are used clinically in the assessment of fetal wellbeing. By opposing lung recoil, FBM help to maintain the high level of lung expansion that is now known to be essential for normal growth and structural maturation of the fetal lungs. During 'apnoeic' periods between successive episodes of FBM, active laryngeal constriction has the effect of opposing lung recoil by resisting the escape of lung liquid via the trachea. The prolonged absence or impairment of FBM is likely to result in a reduced mean level of lung expansion which can lead to hypoplasia of the lungs. There is clinical evidence, disputed by some, that the absence of FBM exacerbates the effects of other factors that are associated with lung hypoplasia, such as premature rupture of fetal membranes and oligohydramnios. Even in the absence of such factors, prolonged or repeated reductions or abolition of FBM may contribute to impairments of fetal lung development; FBM can be inhibited by fetal hypoxaemia, hypoglycaemia, maternal alcohol consumption, maternal smoking, intra-amniotic infection and maternal consumption of sedatives or narcotic drugs. Abnormal growth of the fetal lungs has relevance for postnatal respiratory health as it is now recognised that there may be only a limited capacity after birth for the restoration of normal pulmonary architecture following impaired intra-uterine lung development.

Animals↗
PubMed2002

Polymorphisms in the promoter region of the neutrophil elastase gene are associated with lung cancer development.

Neutrophil elastase (NE) is a powerful serine protease capable of degrading most protein components of the extracellular matrix. We hypothesize that this elastase may play a significant role in lung cancer development and tested our hypothesis in a study of 348 primary lung cancer cases and 299 controls. Analysis of the entire gene using denaturing high performance liquid chromatography identified two novel single nucleotide polymorphisms (SNPs) in the promoter region: -903 T or G (REP-a) and -741 G or A (REP-b). Allele frequencies of these two SNPs were compared between the cases and controls using chi(2) statistics. The estimated relative risk in association with the TT at REP-a or the GG at REP-b was measured by odds ratio. Individuals with -903TT or -741GG allele had a 2.3 and 1.4 times higher risk of developing lung cancer than those with TG or AA+AG alleles, respectively. The relative risk for the combined effects of both high-risk alleles at REP-a and REP-b, i.e., TT-GG type, was 24.8. Functional association of the two markers with cancer risk was examined by luciferase activity of the promoter containing different SNPs. We demonstrated a 1.9-fold relative luciferase activity in the promoter construct with -903T/-741G (T-G) compared with the -903G/-741A (G-A) in A549 human non-small cell lung cancer cells, providing evidence that the TT-GG type correlates with a high NE level. In conclusion, our findings support an etiological role of NE in lung cancer development.

Adult↗
PubMed2005

Persistent vascular defects in lung allografts attributed to defective endogenous endothelial progenitors.

BACKGROUND: A major pathological finding in human newborns with pulmonary hypoplasia and congenital diaphragmatic hernia is the presence of vascular abnormalities in lungs. Vasculogenesis/angiogenesis are crucial to lung development. To study lung alveolar development, including microvascular formation in fetal lung implants, Schwarz et al. [1] developed a subcutaneous allograft model. We adopted their model to assess the influence of neovascularization or the "host-graft vascular development" on hypoplastic lung structure and growth. MATERIALS AND METHODS: Normal and hypoplastic lungs at pseudoglandular stage were implanted subcutaneously under the dorsolateral fold of immunocompromised nude mice (athymic, nu/nu). Lung allografts were removed and assessed at 2, 4, 6, and 8 weeks postimplantation. RESULTS: Neovascularization of implanted lungs from subcutaneous vasculature of nude mice resulted in varying degrees of maturation of implanted normal and hypoplastic lungs. By 4 weeks, implanted normal lungs contained Type 2-like cells and by 7 to 8 weeks, Type 2 and Type 1-like cells, air spaces had enlarged, and surfactant secretion was observed. Despite some differentiation and maturation of hypoplastic lungs, there was more mesenchymal tissue, no secondary septa, and smaller air spaces compared to normal lungs. CONCLUSIONS: (a) Neovascularization or host-graft vascular development occurs in both normal and hypoplastic lung allografts. (b) Development and maturation of implanted normal and hypoplastic lungs follow the establishment of the vascular connections between the host and grafts. (c) The host-graft vascular connections do not improve the growth of normal or hypoplastic lungs. (d) Neovascularization failed to overcome the embryonic defects in vascular formation and the pulmonary vasculogenesis remained defective in hypoplastic lung allografts, which may be attributed to the defective endogenous endothelial progenitor cells.

Animals↗
PubMed1998

Antagonistic effects of dexamethasone and retinoic acid on rat lung morphogenesis.

We have reported that dexamethasone (DEX) treatment of early embryonic rat lungs in culture induced features of both distorted and accelerated maturation. In this report, we investigated the effects of retinoids on normal and DEX-induced lung development in vitro. Lung maturation was assessed by examining the morphology and the expression of genes related to epithelial differentiation (surfactant proteins, SP-A, SP-B and SP-C and Clara cell protein, CC10) and growth [keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF)]. We cultured d 14 and 15 fetal rat lungs in the presence of DEX (1-1000 nM) and/or all-trans-retinoic acid (RA) (10(-7)-10(-5) M) for 4 d. RA at 10(-6) and 10(-5) M inhibited branching and dilated the distal tubules, and at 10(-5) M caused dilatation of the proximal tubules destined to form the trachea and the main bronchi. The adverse effects of DEX, such as distorted branching, tubular dilatation, and suppression of both lung growth and epithelial cell proliferation, were all prevented by RA. In addition, RA inhibited several features of DEX-induced accelerated maturation, such as: 1) the increased levels of SP-A, SP-B, and CC10 mRNAs; 2) the attenuation of mesenchymal tissue; and 3) the mature distribution of cells expressing SP-C mRNA. In contrast, RA potentiated the increase of KGF and decrease of HGF transcripts induced by DEX. In conclusion, the study shows antagonism by RA of DEX-induced effects on lung morphology and gene expression. We postulate that normal lung development requires a balanced action of endogenous retinoids and glucocorticoids.

Animals↗
PubMed1988

Characterization of the glucocorticoid receptor in fetal rat lung during development: influence of proteolytic activity.

Glucocorticoid receptor (GR) from fetal rat lung cytosol was characterized during development. A gradual increase in receptor concentration without an apparent change in ligand affinity was observed during ontogenesis (16-20 days of gestation). GR was present at least 2 days prior to gestational day 18, from which day maternal betamethasone administration stimulated choline chloride incorporation into phosphatidylcholine, the major phospholipid in surfactant. Gel permeation analysis of lung cytosolic GR from fetuses of different gestational ages showed a gradual disappearance of a 3.6 nm GR seen in day 16 cytosol and to the appearance of a 5.8 nm GR in cytosol from day 19. The differences in Stokes' radii of GR were not due to transcriptional or posttranscriptional modifications of the GR transcript, since both day 16 and day 19 fetal lung contained a 7 kb GR mRNA similar to that in adult rat lung. Mixing experiments showed that the 3.6 nm GR was generated by an increased proteolytic activity in day 16 lung tissue. Preservation of a normal size 5.8 nm in day 16 fetal lung upon extraction could only be achieved by preincubating and homogenizing the lung tissue in the presence of protease inhibitors. No protease activity was found in day 16 cytosol suggesting the presence of a rapidly inactivated protease(s). The protease activity responsible for GR degradation was probably of a serine protease type, since proteolytic activity could be inactivated by diisopropylfluorophosphate alone, a potent inhibitor of serine proteases. From these results we conclude that: (i) the observed differences in Stokes' radii between GR from fetal lung of different developmental stages is attributable to proteolysis following extraction, most likely by a rapidly inactivated serine protease. This activity diminished during fetal lung development. However, in intact lung cells, GR is physicochemically identical throughout development; (ii) the lack of glucocorticoid stimulation or surfactant synthesis on day 16 and 17 in fetal rat lung despite the presence of low concentration of GR is therefore not explained by any differences in GR structure.

Animals↗
PubMed2005

Changes in fetal lung distension alter expression of vascular endothelial growth factor and its isoforms in developing rat lung.

Vascular endothelial growth factor A (VEGF-A) is essential for normal pulmonary vascular and parenchymal development. Changes in fetal lung distension profoundly affect lung growth and maturation, including vascular development. To define developmental lung expression of VEGF-A and its receptors and investigate effects of changes in fetal lung distension, we studied fetal rats at embryonic day (ED) 16, 19, and 22, postnatal rats at postnatal day (PD) 5, 10, and 21, and adult rats. We used reverse transcriptase PCR to measure mRNA expression for VEGF-A isoforms (VEGF-A(120), (-144), (-164), and (-188)) and VEGF-A receptors, Flt-1 and Flk-1. With advancing development, mRNA content increased only for VEGF-A(188) (p < 0.05) and for Flt-1 (p < 0.02) and Flk-1 (p < 0.005). As a percentage of total VEGF-A mRNA, VEGF-A(188) (15% at ED 16) increased to become the dominant isoform at PD 21 (40%, p < 0.005) and adulthood; in contrast, there were decreases in both VEGF-A(144) (p < 0.05) and (-120) (p < 0.005). VEGF-A protein was expressed in alveolar epithelium (type I and II cells) and interstitium. Increasing fetal lung distension by tracheal occlusion (TO) accelerated the normal maturational pattern of VEGF-A isoforms and increased VEGF-A protein; decreasing fetal lung distension by congenital diaphragmatic hernia (CDH) retarded the normal developmental pattern and decreased VEGF-A protein. Neither TO nor CDH consistently affected Flt-1 or Flk-1 mRNA content. These results show that mechanical factors significantly affect lung VEGF-A expression and suggest that VEGF-A mediates previously described changes in lung vascular and parenchymal development caused by CDH and by TO.

Animals↗
PubMed1997

Basaloid squamous carcinoma of the larynx: report of a case.

Basaloid squamous carcinoma (BSC) is a rare neoplasm. We present a case of basaloid squamous carcinoma of the larynx in a 57-year-old male patient. The diagnosis before treatment was supraglottic carcinoma (T3N1MO) and biopsy of the larynx revealed a poorly differentiated squamous cell carcinoma. Total laryngectomy and right radical neck dissection were performed, and pathological studies of a specimen removed from the larynx revealed BSC of the larynx. The patient's postoperative progress was uneventful, however, 12 months later he developed lung metastasis of the left side. The patient underwent partial resection of the lung. He developed recurrence of lung metastasis 6 months later. Chemotherapy with cisplatin (CDDP) and vindesine sulfate (VSD) was administered in two courses, but the efficacy was evaluated as no change (NC). At present, 26 months after the first visit, he has been asymptomatic with lung metastasis, and there was no evidence of recurrence in the neck.

Carcinoma, Basosquamous↗
PubMed2006

Is repetitive wounding and bone marrow-derived stem cell mediated-repair an etiology of lung cancer development and dissemination?

The prevailing view of lung cancer is multi-step progression of normal cells into cancer cells through gain of function oncogenes coupled with loss of tumor suppressor genes. This progression of genetic damage ultimately results in the hallmarks of cancer. This theory has strong support from studies finding genetic damage in early stage preneoplastic lesions in lung epithelial cells from current or former smokers. This paper discusses an alternate theory that lung cancer is a bone marrow stem cell derived disease. Chronic cigarette smoking results in lung inflammation and epithelial damage that activates a chronic wound repair program. Recent studies have demonstrated that ability of bone marrow derived stem cells to respond to epithelial wounding and contribute to epithelial repair. The identification of cancer stem cells that are distinct from the bulk tumor cells through their ability of self-renewal may suggest that such cells are important in the development of lung cancer. The evidence supporting the hypothesis along with its implications are discussed. Confirmation of the hypothesis would suggest that the transition time from a normal cell to overt cancer cell may be much shorter than that based on the multi-step cancer progression model. Additionally, if wounding in other organs is a beacon that attracts bone marrow derived tumor cells, efforts to ameliorate areas of epithelial injury and compensatory wounding may block bone marrow derived tumor cell homing, aberrant repair, and metastasis. Finally, a bone marrow derived lung cancer stem cell would require stem cell poisons for cure.

Bone Marrow Cells↗
PubMed2002

Nitric oxide modulates branching morphogenesis in fetal rat lung explants.

Cells of the developing lung express the constitutive nitric oxide synthases (NOSs) I and III. The developmental importance of these enzymes is largely unknown, although a role for nitric oxide (NO) in the regulation of pulmonary blood flow at birth is established. Known effects of NO on transcription factors, apoptosis, and cellular proliferation, plus the time and spatial limits of pulmonary NOS expression, suggest that NO might influence lung development. We tested the potential of NO to modulate lung branching morphogenesis by exposing lung explants from gestational day 13 rat fetuses to varying doses of several NO donors (NONO-ate). We counted the number of airway branches that were added between the first and 72nd h of culture. NO released only from a NONO-ate with a long half-life [(Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]-diazen-1-ium-1,2-diolate-NO], increased branching in ambient O(2) by twofold. The NO effect was not mimicked with a cyclic guanine monophosphate analog; nonspecific NOS inhibitors in millimolar concentrations inhibited branching. We conclude that endogenous and exogenous NO can modulate branching morphogenesis in the rat lung.

Animals↗
PubMed1988

Subcellular distribution of disaturated phosphatidylcholine in developing rabbit lung.

To determine the subcellular distribution of disaturated phosphatidylcholine (DSPC) in lung tissue during perinatal development, fetal rabbits at 24, 26, 28 and 31 (term) days gestation and newborns were studied. Following alveolar lavage, fractions enriched in nuclei-cellular debris, mitochondria, microsomes, surfactant (lamellar bodies) and cytosol were prepared from the residual tissue homogenate, and their DSPC content was determined. The DSPC content of the unfractionated residual lung tissue homogenate progressively and significantly increased during fetal development, rising from 9.09 +/- 0.91 to 17.45 +/- 2.88 mg/g dry lung between 24 days gestation, and term. Between 24 and 26 days gestation the overall increase in tissue DSPC was due to a two-fold increase in the mitochondrial, microsomal and cytosolic pools. Lamellar bodies were first isolable at 26 days gestation. The DSPC content of this fraction increased six-fold (from 0.10 +/- 0.02 to 0.67 +/- 0.15 mg/g dry lung) between 26 and 28 days gestation and a further seven-fold (to 4.63 +/- 1.06 mg/g dry lung) by term, accounting for the overall increase in the tissue homogenate value during this time period. By the first postnatal day, microsomal and cytosolic DSPC increased another two-fold, but no significant change occurred in the other subcellular fractions. Alveolar lavage DSPC progressively increased over the time period studied. While there was no change in the lamellar body DSPC/total PC ratio during fetal development, each of the mitochondrial, microsomal and cytosolic ratios decreased between days 26 and 28 of gestation and then increased at term.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Total exclusion from external respiration protects lungs from development of fibrosis after paraquat intoxication.

Most survivors of paraquat intoxication go on to develop fibrosis of the lung leading to death within a few weeks. The pathogenic effects of paraquat are based on the formation of oxygen free radicals. A cascade reaction occurs at the cell membrane which is damaged and cell integrity is destroyed. Fibroblasts migrate into the damaged region leading to the laying down of collagen and subsequent fibrosis. Currently paraquat intoxication is treated with gastrointestinal lavage, haemoperfusion and haemodialysis with mixed results. Artificial respiration with low percentage of inspired oxygen is instituted in order to decrease the possible release of oxygen radicals. However, in most cases, developing fibrosis prevents this treatment continuing and requires increased concentrations of inspired O2 and increased ventilation pressure. The combination of increased FiO2 and barotrauma leads to a vicious circle of parenchymal lung damage. In this study we present a treatment designed to avoid the development of lung fibrosis using total exclusion of segments of the lung from external ventilation. Exclusion from external ventilation was performed in animal experiments by instillation of Ethibloc, an amino acid glue, in one main bronchus to create an atelectasis. In different experimental groups this procedure was performed before and after intraperitoneal intoxication with paraquat. Four to twelve days later the experimental animals were sacrified and the ventilated lungs and the atelectatic lungs were compared. The ventilated lungs showed dose-dependent damage to the alveolar epithelium and gross interstitial oedema. In some cases fibrosis was seen. The atelectatic parts of the lung were not different from the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Changes in lung elastic fiber structure and concentration associated with hyperoxic exposure in the developing rat lung.

Prolonged hyperoxic exposure is associated with impaired alveolarization of the lung in both the rat and the human neonate. Elastin is currently thought to play a pivotal role in the alveolarization of the lung by providing the structural framework around which new alveoli will develop. Previous studies in both the rat and the human neonate have demonstrated a risk for proteolytic destruction of lung elastin associated with prolonged hyperoxic exposure. The present study was undertaken to determine whether continuous exposure to 100% oxygen during the period of alveolar development in the rat (Days 4 to 13) would alter lung elastin. Parenchymal lung elastic fiber length, volume density of parenchyma, mean linear intercept, and internal surface area were quantitated using morphometric techniques, and the values were compared in control, oxygen-exposed, and malnourished rat pups. Stereologic measurements indicated that total elastic fiber length was significantly greater in lungs of control pups than in lungs of either the oxygen-exposed or the malnourished pups. Examination of sections of lung tissue 20 to 30 microns thick indicated altered elastic fiber structure and numerous alveolar fenestrae only in the hyperoxic pups. The results of these studies demonstrated that hyperoxic exposure during alveolarization alters both total length and structure of lung elastic fibers and suggest that impaired lung development might be due in part to these observed changes.

Animals↗
PubMed2001

Morphological analysis of the postnatally developing marsupial lung: The quokka wallaby.

We investigated the events that take place during the postnatal morphogenesis of the lung of the quokka wallaby, Setonix brachyurus, using the light microscope and both the scanning and transmission electron microscopes. The lung of term, newborn babies (joeys) at 3-days of postnatal life was at late canalicular stage and comprised large airways and tubules separated by thick mesenchymal interstitium. The tubules were lined by a low cuboidal epithelium but had few portions with true gas exchange barrier where capillaries came into close contact with squamous type of epithelium. By the fifth day postpartum, the lung entered the early saccular stage characterised by large air sacs, thinner septa, a better developed double capillary system and conversion of the cuboidal epithelium into a squamous one of type I cells interrupted by groups of cuboidal type II cells with lamellar bodies. Transitory respiratory bronchioles were recognisable toward the end of this stage. Formation of secondary septa started by Day 15, dividing the saccules into several generations of smaller air spaces. There were alternating and concurrent periods of tissue proliferation and air space expansion, followed by septal thinning. Alveolization started from about 125 days postpartum when the first burst of small sized air spaces bounded by septa with a single capillary layer were encountered. By Day 180 the process of alveolization was completed with only occasional septa showing a double capillary system and by Day 210 postnatally, the lung resembled that of an adult. For the first time in a mammal, the canalicular stage was encountered postnatally during lung development.

Age Factors↗
PubMed1998

Effects of maternal vitamin A status on fetal heart and lung: changes in expression of key developmental genes.

Vitamin A is required during pregnancy for fetal lung development. These experiments monitored fetal lung morphology in normal and vitamin A-deficient rats. The expression of elastin and the growth arrest-specific gene 6 (gas6) in fetal and neonatal hearts and lungs was assessed by Northern blotting. In normal-fed rats, elastin and gas6 were expressed in the fetal lung and heart from day 19 of gestation up to day 2 postnatally. Maternal vitamin A deficiency altered fetal lung development. On day 20, the bronchial passageways were less developed and showed reduced staining for elastic fibers, and in the neonates, the relative air space and the size of the sacculi were reduced. In the fetal lung, the mRNAs for elastin and gas6 were reduced to 56 and 68% of the control values, respectively. In the fetal heart, the mRNA for elastin was reduced to 64% of the control value, whereas gas6 was increased twofold. In the neonate, there was no change in elastin expression in the lung or heart, but gas6 expression in the heart was increased twofold. These results suggest that, in the pregnant rat, vitamin A deficiency may retard fetal lung development or influence the differentiation of critical cell lines. The changes in elastin and gas6 expression may be used to identify the cell types affected.

Animals↗
PubMed2006

Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice.

Lung development is associated with a surge in surfactant phosphatidylcholine (PC) production to prepare the newborn for extrauterine breathing. This process is associated with a marked increase in the activity of the rate-regulatory surfactant enzyme, CTP:phosphocholine cytidylyltransferase (CCTalpha). To investigate the molecular basis for developmental activation of CCTalpha, we analyzed expression of endogenous CCTalpha and a reporter gene, beta-galactosidase, in fetal, newborn, and adult promoter-reporter transgenic mice. Transgenics harboring approximately 2 kb of the CCTalpha promoter linked upstream of a beta-galactosidase reporter gene displayed relatively high expression in distal lung epithelia. Endogenous lung CCTalpha and beta-galactosidase activities, protein content, and transcript levels displayed maximal expression within the newborn period. CCTalpha and beta-galactosidase activities and enzyme levels increased with time in cultured fetal lung explants isolated from transgenics. Transfectional analysis using CCTalpha promoter-reporter constructs in developing rat type II cells revealed that a region encompassing -169/+71 contained the DNA elements required for perinatal activation. The studies demonstrate that developmental induction of surfactant phospholipid is due, at least in part, to transcriptional activation of the CCTalpha gene.

Animals↗