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P L Ballard

Publications and source records attributed to P L Ballard.

At least 19 recordsLinked to original sources
PubMed1998

Targeting type II and Clara cells for adenovirus-mediated gene transfer using the surfactant protein B promoter.

We examined the ability of the human surfactant protein B (SP-B) promoter to confer cell specificity of transgene expression in an adenoviral vector. Using similar replication-deficient adenoviruses (rAd), we compared lacZ reporter gene expression driven by the human SP-B promoter (rAd.SPBlacZ) with the ubiquitously expressed Rous sarcoma virus promoter (rAd.RSVlacZ). rAd.SPBlacZ expressed lacZ in H-441 and A549 lung epithelial cell lines and not in HeLa cells whereas rAd.RSVlacZ expressed in all three cell lines. In primary human fetal lung fibroblasts, beta-galactosidase activity from rAd.RSVlacZ transduction increased in a dose-dependent manner whereas activity from rAd.SPBlacZ remained low. In mixed cell cultures prepared from human fetal lung explants that contained fibroblasts and type II cells, X-Gal staining localized rAd.SPBlacZ expression to only type II cells whereas rAd.RSVlacZ expressed in both cell types. In 24-wk gestation human fetal tissue explants infected ex vivo, the RSV promoter directed lacZ expression in lung, trachea, heart, liver, and esophagus, whereas with the SP-B promoter lacZ was expressed only in lung, specifically in air space-lining cells. This specificity was maintained in vivo. lacZ expression was undetectable in lung and other tissues after intravenous administration of rAd.SPBlacZ whereas rAd.RSV-lacZ expressed primarily in liver. After intratracheal instillation of rAd.SPBlacZ into mice, X-Gal staining localized expression to type II and Clara cells. In contrast, rAd.RSVlacZ expressed in all pulmonary epithelial cell types. Our results indicate that the SP-B promoter may be useful in targeting type II and Clara cells for gene therapy of conditions such as inherited deficiency of SP-B.

Adenocarcinoma↗
PubMed1997

Phorbol ester down-regulation of lung surfactant protein B gene expression by cytoplasmic trapping of thyroid transcription factor-1 and hepatocyte nuclear factor 3.

The lung-specific surfactant protein B (SP-B) is essential for surfactant function and normal respiration. We investigated the role of thyroid transcription factor-1 (TTF-1) and hepatocyte nuclear factor 3 (HNF3) in the down-regulation of SP-B gene expression by phorbol ester in pulmonary adenocarcinoma H441 cells. Responsiveness to 12-O-tetradecanoylphorbol-13-acetate (TPA) localized to the SP-B proximal promoter (-140/-65 bp) and specifically to binding sites for TTF-1 and HNF3, which act as cell-specific enhancers of SP-B expression. Treatment of cells with TPA (10 nM) caused a time-dependent decrease in both TTF-1 and HNF3 in nuclear extracts and accumulation of both factors in the cytoplasm as assessed by electromobility shift, Western, Southwestern, and immunofluorescence assays. Treatment did not alter the mRNA content or DNA binding activity for either transcription factor. We conclude that down-regulation of SP-B gene expression by phorbol ester involves cytoplasmic trapping and loss of TTF-1 and HNF3 from the nucleus. This mechanism of action is independent of AP-1 and other transcription factors known to be influenced by phorbol ester.

Animals↗
PubMed1997

Transcriptional regulation of surfactant proteins SP-A and SP-B by phorbol ester.

Phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) activate protein kinase C and have been previously shown to down-regulate surfactant proteins SP-A and SP-B in H441 adenocarcinoma cells. We used H441 cells and human fetal lung to further study the mechanism of TPA action and to examine physiologic relevance. In H441 cells, TPA (10 nM) treatment for 24 h decreased SP-A mRNA content to approximately 5% of control cells, with half-maximal effect at approximately 0.5 nM, and reduced SP-A gene transcription rate to 28% of control after 8 h exposure. In cells cultured in the presence of dexamethasone, which increases the low basal level of SP-B expression, TPA decreased both SP-B mRNA content (approximately 8% of control) and rate of transcription (7% of control). In cultured human fetal lung explants, TPA decreased SP-A and SP-B protein and mRNA in a time- and dose-dependent fashion, with half-maximal effect on mRNAs at approximately 3 nM and approximately 50% inhibition after 24 h of exposure, and similarly reduced SP-A and SP-B gene transcription (approximately 55% of control at 8-24 h). We conclude that TPA acts primarily at the level of gene transcription to down-regulate both SP-A and SP-B in H441 and fetal lung cells, and we speculate that inflammatory and other agents that act through PKC may modulate expression of the surfactant proteins and alter surfactant function in vivo.

Culture Techniques↗
PubMed1997

Enhanced distribution of adenovirus-mediated gene transfer to lung parenchyma by perfluorochemical liquid.

Although gene therapy holds great promise for the treatment of inherited and acquired diseases of the lung, a number of issues including efficient delivery and distribution of genes to pulmonary target cells must still be addressed. In this study we evaluated the use of perfluorochemical (PFC) liquid as a vehicle for delivery of recombinant adenovirus (AdCBlacZ) to lungs of juvenile rabbits. Virus was instilled into trachea of rabbits, and 4 days later the lungs were removed, cut into multiple pieces, and assayed for beta-galactosidase (beta-Gal) activity. Total lung expression of the beta-Gal reporter gene was increased two- to three-fold by instillation of the virus (10(11) particles/kg body weight) in saline (1.5 ml/kg) simultaneously with perflubron liquid (15 ml/kg) compared to virus+saline alone (control). Uniformity of beta-Gal activity between lobes was significantly improved by the PFC liquid. In perflubron-treated lungs approximately 45% of the lung pieces had beta-Gal-specific activity values within 50-150% of the mean specific activity for the total lung, compared to only approximately 15% of the pieces in control lungs. More of total lobar beta-Gal activity was recovered in the distal lung tissue (approximately two-fold greater than controls, p < 0.05). Morphological assessment of X-Gal-stained, fresh-frozen lung sections showed increased levels and more complete staining of alveolar wall cells in the PFC group. These data indicate that the PFC liquid perflubron enhances distribution of virus-mediated gene expression to the lung parenchyma in healthy rabbits. PFC liquid may be a useful treatment vehicle for accessing distal spaces of the damaged or diseased lung.

Adenoviridae↗
PubMed1997

Glucocorticoid regulation of surfactant components in immature lambs.

To assess effects of dose and duration of glucocorticoid exposure on maturation of the fetal lung, we administered single or multiple doses of betamethasone (0.5 mg/kg im) to pregnant sheep for 2 or 21 days before preterm delivery at 125 days of gestation. Lung function (compliance, lung volume at 40 cmH2O pressure, and ventilatory efficiency index) was increased after two to four weekly doses of glucocorticoid (2.5- to 4-fold increase) and after 48 h of exposure (1.4- to 2.3-fold). Total protein of lavage fluid decreased similarly with three doses, four doses, and 48 h of treatment. In lambs with long-term exposure to betamethasone, there was a similar, dose-dependent increase in concentrations of saturated phosphatidylcholine and surfactant proteins A (SP-A) and B (SP-B) (maximal 2- to 3-fold in tissue and 10- to 15-fold in lavage fluid). Levels of SP-A and SP-B were closely correlated in lavage fluid. In animals treated for 48 h, only tissue SP-B was increased (2.7-fold). We conclude that 48 h of glucocorticoid treatment improves lung function in the premature lamb without a detectable increase in lavage surfactant components and that longer exposure to antenatal glucocorticoid increases surfactant lipid and proteins in a coordinated fashion. The enhanced response with repetitive dosing indicates that the process of glucocorticoid-induced lung maturation is either reversible and/or gestational age dependent.

Animals↗
PubMed1997

Combined effects of fetal beta agonist stimulation and glucocorticoids on lung function of preterm lambs.

We asked whether a single-dose fetal treatment strategy using betamethasone plus either a long-acting beta 2 agonist (formoterol) or betamethasone plus agents that elevate intracellular cyclic adenosine monophosphate (isobutyl methylxanthine and dibutyryl-cyclic adenosine monophosphate) would augment the effects of prenatal betamethasone on postnatal lung function. Preterm lambs were treated with 0.5 mg/kg beta-methasone or betamethasone plus the other agents and delivered 48 h after treatment. The postnatal lung function as assessed by compliance, ventilatory efficiency, and lung volumes at 40 min of age was improved by prenatal betamethasone and improved further by combination treatment, although the augmented responses were not significantly greater than with betamethasone alone. Fatty acid synthase protein and enzymatic activity were not increased by betamethasone or combined treatments, in contrast to responses reported for other animal models. There were no effects of glucocorticoids or the combined treatments on surfactant. Stimulation of the beta 2 agonist system did not augment postnatal lung function significantly above that noted for betamethasone alone with the agents, doses, and duration of exposures tested.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Expression and glucocorticoid regulation of surfactant protein C in human fetal lung.

The hydrophobic surfactant protein C (SP-C) is known to modulate the biophysical properties of surfactant phospholipid. Although SP-C mRNA has been demonstrated in human fetal lung, there is limited information regarding developmental expression and processing of proSP-C protein. Two epitope-specific human proSP-C antisera, anti-hCPROSP-C (His59-Ser72) and anti-hCTERMSP-C (Gly162-Gly175), were generated to complement previously produced anti-NPROSP-C (Met10-Gln23) for the study of proSP-C expression in human fetal lung. Western blotting and immunocytochemistry detected expression of proSP-C protein by 12-16 wk of gestation. ProSP-C immunoreactivity of preculture lung, limited to expression of proSP-C21 in airway epithelial cells, was markedly enhanced by culture of lung explants in dexamethasone. To examine synthesis of proSP-C, homogenates from explants were labeled with 35S-Met/Cys for 0.5-4 h. Immunoprecipitation with anti-NPROSP-C detected 35S-proSP-C21 by 30 min and, after 2 h of labeling, there was a 15-fold increase in 35S-proSP-C21 in dexamethasone-treated lungs versus controls. Synthesis of proSP-C21 was followed by the appearance of a 24-kD form and smaller processing intermediates including 6-10-kD forms. Posttranslational processing of proSP-C21 was not observed in control explants. SP-C(6-10) were not recognized by either anti-CPROSP-C or anti-hCTERMSP-C. These results indicate that low level expression of proSP-C protein first occurs in epithelial cells early in the second trimester and that expression can be enhanced by dexamethasone. Initial posttranslational processing of human proSP-C involves modification of proSP-C21 to SP-C24 and subsequent proteolysis of C-terminal propeptide domains. We speculate that absence of low Mr intermediates in unstimulated second trimester fetal lung tissue reflects developmental and glucocorticoid dependent regulation of proSP-C21 synthesis and posttranslational processing.

Antibodies, Anti-Idiotypic↗
PubMed1996

Transcriptional regulation of human pulmonary surfactant proteins SP-B and SP-C by glucocorticoids.

Expression of the pulmonary surfactant-associated proteins SP-B and SP-C is under both developmental and hormonal regulation. We used human fetal lung to investigate developmental changes and the mechanism of glucocorticoid stimulation of SP-B and SP-C gene expression. There were similar approximately 3-fold increases in SP-B cytoplasmic mRNA content and transcription rate comparing lung samples of 24 wk versus 16 wk gestation. During 5 days of lung explant culture without hormones, the transcription rate increased for SP-B and decreased for SP-C, paralleling changes in mRNA content. Treatment with 100 nM dexamethasone maximally increased transcription of the SP-B gene (approximately 3-fold) and SP-C gene (approximately 11-fold) after 2 and 8 h, respectively, similar to changes in mRNA content. In dose-response studies, the maximal increase in transcription rate occurred at approximately 10 nM dexamethasone for SP-B and at > or = 100 nM for SP-C. Induction of SP-B mRNA content and transcription rate were not affected by prior cycloheximide exposure, whereas induction of SP-C mRNA was decreased by as little as 1 h exposure to inhibitor. We conclude that glucocorticoids, acting directly in type II cells, regulate the SP-B and SP-C genes primarily at the level of transcription. Induction of SP-C, but not SP-B, requires ongoing protein synthesis which likely reflects involvement of a labile transcription factor. The difference in glucocorticoid sensitivity may indicate that the two surfactant protein genes contain glucocorticoid response elements with different affinities for receptor.

Anti-Inflammatory Agents↗
PubMed1996

Regulation of surfactant protein D in human fetal lung.

Surfactant protein D (SP-D) is a collagenous glycoprotein, produced by lung type II cells, that has structural and functional similarities with SP-A. In this study we postulated that SP-D and SP-A gene expression are regulated in a similar fashion to provide a coordinated local immune defense response to pulmonary infection. We determined content of SP-D protein and mRNA in second-trimester fetal lung and in postnatal tissue by protein blotting and hybridization analyses. Low levels of SP-D mRNA and protein were detected at 16 wk gestation, before appearance of SP-A, and levels increased during gestation. The content of SP-D did not change during 5 days of explant culture, whereas SP-A increased manyfold. Dexamethasone treatment during culture increased SP-D mRNA and protein about 2-fold with maximal response after 1 to 3 days' exposure to 100 nM steroid; under the same conditions SP-A mRNA content is inhibited. There was no significant change in SP-D mRNA after treatment of explants with adenosine 3',5'-monophosphate (cAMP) analog or interferon-gamma, agents which increase SP-A gene expression, nor after exposure to phorbol ester, tumor necrosis factor-alpha, or lipopolysaccharide at concentrations that reduced levels of SP-A mRNA by approximately 50%. We conclude that SP-D in the human lung is under developmental and glucocorticoid regulation occurring at a pretranslational level. SP-D is not influenced by inflammatory mediators that regulate SP-A, suggesting that these two proteins are not coordinately regulated in response to lung infection.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Characterization of the promoter of human pulmonary surfactant protein B gene.

Pulmonary surfactant protein B (SP-B) is required for normal surfactant function and for survival at birth. To further study SP-B gene expression, we sequenced genomic clones and examined promoter activity of SP-B DNA fragments by transient transfection. A plasmid construct containing human SP-B fragment -1039/+431 linked to chloramphenicol acetyltransferase (CAT) reporter gene was readily expressed in H441 cells, which are derived from a human lung adenocarcinoma, but was < 4% as active in Hep G2, HeLa, and Calu 6 cell lines. SP-B promoter activity in H441 cells was orientation dependent and increased by linked Rous sarcoma virus (RSV) enhancer and was stronger than for thymidine kinase (tk) and RSV promoters. Deletional mapping of the 5' flanking region with exonuclease III suggested nonspecific negative (-811/-1039)- and positive (-453/-641)-control regions and a cell-specific enhancer region at -208 to -54. When a fragment from -403 to -35 base pairs (bp) was placed upstream or downstream of tkCAT, in either orientation, expression in H441 cells but not other cell lines was increased 4- to 28-fold relative to tkCAT. Deletional analysis of the 3' terminus indicated a requirement for at least 7 bp 3' of the transcription start site. Promoter activity was strongly inhibited in a dose-dependent fashion by phorbol ester, with responsiveness mapped to bp -208/-54, but was not responsive to glucocorticoid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Adenovirus-mediated gene transfer to human fetal lung ex vivo.

Gene therapy of the fetus or newborn infant is a potentially useful approach for prevention or treatment of specific lung diseases. To begin to address issues such as efficiency, duration, and cellular distribution of transgene expression, we studied transduction of human lung cells by recombinant, replication-deficient adenovirus containing the lacZ gene driven by the beta-actin promoter and cytomegalovirus enhancer (H5.010CBlacZ). Human fetal lungs of 20- to 24-wk gestation received approximately 10(11) viral particles by instillation into a major bronchus, and the tissue was cultured as explants in serum-free Waymouth's medium. beta-galactosidase staining (X-gal) was detected by 24 h in defined regions of treated tissue and localized to epithelial cells of airways and terminal saccules. beta-galactosidase activity in homogenate of treated tissue was maximal 3-5 days after exposure to virus, ranging from 0.2 to 1.5 A420.min-1.mg protein-1 in four experiments (control values were approximately 0.001). When virus was added directly to lung explants in culture, beta-galactosidase was expressed in most of the peripheral cells and rarely in interior cells, the level of activity was dose dependent between 10(8) and 10(11) viral particles/ml, and transgene expression was sustained for at least 28 days. Treatment of isolated cultured cells with virus resulted in equivalent staining of both epithelial cells and fibroblasts. We conclude that fetal lung cells are efficiently transduced by recombinant adenovirus, indicating the feasibility of gene therapy in the infant or fetus. Cultured fetal lung may be useful for testing gene constructs being considered for therapy.

Adenoviridae↗
PubMed1995

Elemental composition of lamellar bodies from fetal and adult human lung.

Previous studies in the rat using electron probe microanalysis have suggested that most of the Ca2+ in alveolar space is probably derived from secreted lamellar bodies (LB). However, the LB Ca2+ content in cultured rat type II cells is low and unaltered by dexamethasone supplementation. In this study, we examined LB Ca2+ content in adult human lung and cultured explants of fetal lung treated with hormones to promote type II cell differentiation. Lung tissue of 20 to 24 wk of gestation was cultured for 4 to 6 days without hormone and with dexamethasone (10 nM), triiodothyronine (2 nM), 8-bromo-cyclic adenosine monophosphate (0.1 mM), or their combinations. The cultured tissue samples were processed for light and electron microscopy or rapidly frozen and stored in freon-22 under liquid nitrogen. Thin cryosections from the frozen samples were prepared and examined using the electron probe microanalysis. Human lung tissue up to 24 wk of gestational age had no detectable LB before explant culture. Explants cultured for 4 days without hormone supplementation (control) had no detectable LB, single-hormone treatments resulted in small LB, and combination treatments resulted in the formation of many large LB in explant type II cells. Despite such morphologic changes, LB Ca2+ in both control and hormone-treated explants was low (overall mean, 4.1 +/- 0.6; P < 0.05) compared with LB of in situ rat and adult human lung (30 +/- 2 and 27 +/- 1.5 mmol/kg dry wt, respectively) and was similar to that found in cultured rat type II cells. LB phosphorus and sulfur under all explant culture conditions were comparable. These observations indicate that human and rat LB elemental compositions are similar and that optimal in vitro conditions with respect to LB Ca2+ metabolism have not been established.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

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.

Adult↗
PubMed1995

Partial deficiency of surfactant protein B in an infant with chronic lung disease.

OBJECTIVE: To evaluate components of pulmonary surfactant and identify mutations in the surfactant protein B gene (SP-B) of a term infant with severe respiratory distress and chronic lung disease. PATIENT AND TESTING: Respiratory distress developed in an infant delivered at term, and he required extracorporeal bypass support for 2 weeks. Until his unexpected death at 9.5 months, he was ventilator and oxygen dependent and required continual dexamethasone therapy. Tracheobronchial lavage samples were analyzed for content of surfactant proteins (SPs), and DNA from blood samples were sequenced and analyzed by polymerase chain reaction restriction analysis for the presence of SP-B gene mutations. Surfactant lipid composition and function, the contents of SPs and their messenger RNAs (mRNAs), and the immunostaining pattern for SPs were determined in postmortem lung tissue. RESULTS: The lavage sample contained SP-A but not SP-B, and DNA restriction analysis indicated that the patient and his mother were heterozygous for the previously described 121ins2 mutation of SP-B. Postmortem lung tissue contained normal levels of SP-A and its mRNA, a low but detectable level of SP-B, and near normal content of SP-B mRNA. SP-C was abundant on staining, and some 6-kd precursor was present in tissue. A surfactant fraction was deficient in phosphatidylglycerol and was not surface active. On DNA sequencing, a point mutation was found in exon 7 of the patient's SP-B gene allele without the 121ins2 mutation, resulting in a cysteine for arginine substitution, and the father was a carrier for the same mutation. CONCLUSIONS: We describe a patient who is a compound heterozygote with a new mutation and only a partial deficiency of SP-B. Some forms of inherited SP-B deficiency may have low expression of immunoreactive and possibly functional SP-B with milder lung disease and longer survival. These infants may benefit from glucocorticoid therapy and may not develop antibodies to SP-B after either lung transplant or gene therapy.

Alleles↗
PubMed1994

Glucocorticoid and cAMP increase fatty acid synthetase mRNA in human fetal lung explants.

During late fetal development, synthesis of surfactant phospholipid requires a large supply of fatty acid precursor. Fatty acid synthetase is a regulatory enzyme for de novo fatty acid synthesis in lung as well as other lipogenic tissues. In this study, we report hormonal induction of FAS mRNA in human fetal lung explants (16-23 week gestation) cultured up to 7 days in Waymouth's medium (no serum) supplemented with dexamethasone (Dex, 10 nM) or agents that increase cAMP (8-Br-cAMP, 0.1 mM; isobutylmethylxanthine, 0.1 mM; forskolin, 0.01 mM; PGE1, 0.01 mM). Exposure of explants to Dex or cAMP agents increased FAS mRNA content by 6 h and maximal stimulation occurred at 72 h for Dex (approx. 3-fold increase) and 24 h for cAMP (approx. 2-fold increase). In the presence of both Dex and cAMP there was a synergistic increase in FAS mRNA content at all times (approx. 11-fold increase at 72 h). Induction of FAS mRNA was specific for steroids with glucocorticoid activity, reversible on removal of hormone, and was half-maximal at 2-3 nM Dex consistent with receptor mediation. Actinomycin D blocked induction by Dex but not by cAMP suggesting a transcriptional effect by glucocorticoid but not by cAMP. T3, which increases phosphatidylcholine synthesis, did not induce FAS mRNA. The findings indicate that both glucocorticoid and cAMP increase FAS gene expression consistent with an important role for FAS in regulating the supply of fatty acid for surfactant phospholipid synthesis.

Cyclic AMP↗
PubMed1993

Hormonal regulation of cholinephosphate cytidylyltransferase in human fetal lung.

Cytidylyltransferase (CTP: cholinephosphate cytidylyltransferase, EC 2.7.7.15, CYT) is a regulatory enzyme for synthesis of pulmonary surfactant phosphatidylcholine (PC). The effects of glucocorticoid, T3, and cAMP on CYT activity were studied in explants of human fetal lung (18-22 weeks gestation) cultured for 1-6 days in serum-free medium. Dexamethasone (Dex, 10 nM) treatment for 5 days increased homogenate CYT activity (+115%, P < 0.02) when assayed in the presence of added lipid co-factor (L-alpha-phosphatidylglycerol, PG, 1.1 mM) and tended to increase activity in its absence (+77%, P = 0.12). Cytosolic activity was also significantly elevated in the presence of added co-factor (+124%, P < 0.01), but there was no effect of Dex on microsomal specific activity. Dex increased the recovery of CYT activity in the cytosolic fraction (75% vs. 43% (control) of the homogenate activity), but not in the microsomal, nuclear or mitochondrial fractions. Assayed in the presence of added co-factor, stimulation of CYT by Dex was apparent after 48 h exposure and maximal by 5-6 days exposure to < or = 30 nM concentration. T3 or agents that increase endogenous cAMP stimulated cytosolic activity by 40% and 36-74%, respectively, after 4-6 days exposure, but none produced an additive increase in the presence of Dex. We conclude that stimulation of CYT activity contributes to hormonal induction of surfactant lipids by each of these hormones. Glucocorticoids may increase the amount of CYT enzyme as well as activate the enzyme via increased synthesis of lipid co-factor.

Choline-Phosphate Cytidylyltransferase↗