Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of adult rats to 85% ambient oxygen increased the content of surfactant proteins SP-A, SP-B, and SP-C recovered from alveolar lavage. The surfactant proteins increased during 1 to 7 d of oxygen exposure. The increased surfactant protein was associated with increased relative abundance of mRNA encoding each of the proteins in lung tissue. Exposure to hyperoxia progressively increased the amounts of the surfactant proteins in alveolar lavage fluid as estimated by immunoblot analysis after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The mRNAs encoding SP-A (1.7 and 1.0 kb), SP-B (1.6 kb), and SP-C (0.9 kb) increased significantly after oxygen exposure for 5 d. The present findings support the concept that oxygen exposure mediates surfactant protein expression at a pretranslational level.
Am J Respir Cell Mol Biol 1991 Feb
PMID:Increased expression of pulmonary surfactant proteins in oxygen-exposed rats. 199 Oct 71

Prenatal administration of glucocorticoids has been shown to enhance surfactant production in the fetus. Since the surfactant proteins play an important role in surfactant function and secretion, we wished to determine the effects of maternal glucocorticoid administration on their fetal expression and appearance. Daily dexamethasone (DEX) (1 mg/kg/day) or 0.9% saline was administered to timed-pregnant rats on gestational days 14 through 16 or on day 16 with sacrifice on day 17 (term day 22), and on gestational days 14 through 18, or days 16 through 18, or day 18 with sacrifice on day 19. SP-A content was determined in lung homogenates from treated and control male and female fetal rats by an enzyme-linked in lung homogenates from treated and control male and female fetal rats by an enzyme-linked immunosorbent assay. The abundance of mRNAs for SP-A, SP-B, and SP-C per fixed amount of total cellular RNA was also determined in lungs from treated and control male and female fetal rats by Northern blot analysis. In litters sacrificed on day 17, DEX administered on days 14 through 16 and on day 16 resulted in significant increases in SP-A content. Expression of SP-A mRNA, which was not detectable in control fetuses on day 17, became clearly apparent after either 1 or 3 d of DEX treatment. The abundance of mRNAs for SP-B and SP-C also increased in day-17 fetuses after either 1 or 3 d of DEX treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Apr
PMID:Effects of maternal dexamethasone on expression of SP-A, SP-B, and SP-C in the fetal rat lung. 201 97

We have studied the relationship between lysosomes and lamellar bodies in alveolar type II (ATII) pneumocytes using a monoclonal antibody (anti-lgp-120) directed against a 120-kD rat lysosomal membrane glycoprotein and a polyclonal antibody (anti-SP-A) directed against rat surfactant protein A. The anti-lgp-120 precipitated a protein molecular mass of 120 kD from Triton cell lysates radiolabeled with [35S]methionine, and the anti-SP-A precipitated surfactant apoprotein A from the medium when analyzed under similar conditions. When ATII cells were cultured on Engelbreth-Holm-Swarm tumor basement membrane, and studied by indirect immunofluorescence, some structures seem to react with both antibodies, and others with only one. ATII cells cultured on plastic showed a major population of large vesicles that were labeled intensely with both antibodies, and a second population of vesicles that were labeled weakly and only with anti-SP-A. Analytical cell fractionation of freshly isolated ATII cells confirmed that lgp-120 was only present in structures containing the lysosomal matrix enzyme N-acetyl-beta-glucosaminidase. In contrast, SP-A was identified in two populations of vesicles with high phospholipid-to-protein ratios: one lacked N-acetyl-beta-glucosaminidase and lgp-120 and contained lamellar bodies; the other contained both lysosomal markers and a heterogeneous population of organelles that included multivesicular bodies, lamellar bodies, and lysosomes. Western blots of trichloroacetic acid precipitates of cell fractions identified proteins within the lysosomal compartment that reacted with anti-SP-A, but whose molecular mass was less than 28 kD. The results indicate that, in ATII cells, surfactant is located in two functionally distinct structures, one of which is probably involved in surfactant secretion, and the other, surfactant degradation. The techniques developed in this study should allow the role of these structures in the secretion and recycling of surfactant to be determined.
Am J Respir Cell Mol Biol 1991 Jun
PMID:The relationship between lamellar bodies and lysosomes in type II pneumocytes. 205 92

We examined the effects of interferon-gamma (IFN-gamma) on development of the surfactant system in alveolar epithelial cells of fetal lung. Explants of second-trimester human fetal lung were cultured for 1 to 6 days in serum-free medium containing recombinant human IFN-gamma (0.03 to 30 ng/ml) and/or dexamethasone (10 or 100 nM). Treatment for 3 days with IFN-gamma alone, dexamethasone alone, and IFN plus dexamethasone increased the content of surfactant protein A (SP-A, 28 to 36 kD) by approximately 3-, 2.5-, and 10-fold, respectively. The biphasic response pattern of SP-A to dexamethasone (stimulation initially and inhibition with continued culture) was not altered by the presence of IFN-gamma. IFN-gamma also stimulated accumulation of SP-A mRNA (2.7-fold at 24 h) but did not affect the levels of mRNAs for surfactant protein B (18 kD) and surfactant protein C (5 kD). To assess the effect of IFN-gamma on synthesis of surfactant lipids, we determined the content of phosphatidylcholine, the rate of labeled choline incorporation into phosphatidylcholine, saturation of newly synthesized phosphatidylcholine, and the activity of fatty acid synthetase, a glucocorticoid-inducible enzyme. Treatment of explants for 5 days with IFN-gamma had no effect on these parameters. Studies by light and electron microscopy revealed little difference between control and IFN-treated explants with regard to cell viability and epithelial cell differentiation. We conclude that IFN-gamma has a selective stimulatory effect on SP-A among surfactant components.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1990 Feb
PMID:Interferon-gamma and synthesis of surfactant components by cultured human fetal lung. 210 32

The synthesis of the major surfactant protein, SP-A, was studied in activated alveolar type II cells isolated from the lungs of rats exposed to silica by intratracheal instillation. Exposure of rats to silica resulted in large increases in the levels of disaturated phosphatidylcholine and SP-A in the extracellular and intracellular surfactant compartments. Isolated type II cells were used to determine if the observed increases in SP-A were associated with increased SP-A synthesis. Type II cells were isolated by a combination of elastase digestion, centrifugal elutriation, and differential adherence on IgG-coated petri dishes. Type II cells from silica-treated lungs were separated into two populations, designated type IIA and type IIB. The type IIB, or activated population, consisted of type II cells that were larger than normal type II cells and, in addition, contained larger and more numerous lamellar bodies than normal type II cells. Type IIB cells contained 4.3-fold higher levels of SP-A compared to normal type II cells. SP-A synthesis was measured by incubating freshly isolated cells with [35S]Translabel (70% [35S]methionine, 15% [35S]cysteine) for up to 4 h in methionine-free medium, followed by immunoprecipitation of newly synthesized protein. The rate of SP-A synthesis was increased approximately 6.7-fold in the activated type II cells. Analysis of the newly synthesized protein by one-dimensional SDS-PAGE indicated three intracellular forms of SP-A with molecular weights of approximately 26,000, 30,000, and 34,000. In type II cells from control rats, the 34-kD protein accounted for approximately 93% of the newly synthesized SP-A after 4 h of incubation; only a small amount of radioactivity was associated with the lower molecular weight species. The increased biosynthesis of SP-A in the activated type II cells was associated with a 7.3-fold increase in the level of SP-A mRNA. These results indicate that the content and synthesis of SP-A are both highly elevated in activated type II cells and that these increases may be due to increased levels of SP-A mRNA.
Am J Respir Cell Mol Biol 1990 Sep
PMID:Induction of surfactant protein (SP-A) biosynthesis and SP-A mRNA in activated type II cells during acute silicosis in rats. 216 98

The pulmonary surfactant apoproteins A, B, and C (SP-A, SP-B, and SP-C, respectively) function in concert with surfactant phospholipids to reduce surface pressure in the alveolus. Surfactant apoproteins also regulate surfactant synthesis, secretion, adsorption, and recycling. SP-A and B have been localized by immunocytochemistry to alveolar epithelial (type II) cells, alveolar macrophages, and nonciliated bronchiolar epithelial (Clara) cells. In contrast, in situ hybridization to SP-A and B mRNA in human lung has shown SP-A and B transcripts in type II cells, but only SP-B message in Clara cells, implying that synthesis of SP-A occurs exclusively in type II cells. In this report, in situ hybridization to SP-A mRNA was performed on adult and developing rabbit lung and on human lung. SP-A transcripts were found in type II cells and bronchiolar epithelium of both species. The distribution of SP-A message-containing cells in the bronchiolar epithelium of rabbits and humans was similar to the distribution of Clara cells in these two species. These data indicate that SP-A is not only synthesized in type II cells but also in Clara cells.
Am J Respir Cell Mol Biol 1990 Nov
PMID:Surfactant apoprotein A (SP-A) is synthesized in airway cells. 222 3

Pulmonary surfactant, which is composed of phospholipids and three lung-specific apoproteins, is synthesized and secreted by alveolar type II cells. Previous work from this laboratory (Biochim. Biophys. Acta 1987; 931:143-156) has shown that cell-extracellular matrix interactions and cuboidal cell shape affect both the ultrastructural appearance and pattern of phospholipids synthesized by cultured rat type II cells. In the present study, we have examined the effects of cell-matrix interactions and cell shape on the ability of adult rat type II cells to express the surfactant apoproteins in culture. Isolated adult rat type II cells were cultured for 2, 4, and 8 days on either tissue culture plastic, on an extract of the Engelbreth-Holm-Swarm (EHS) tumor, or on laminin-coated plastic dishes. Expression of surfactant proteins A, B, and C (SP-A, SP-B, and SP-C) was evaluated by Northern analysis using specific rat cDNA probes for these mRNAs. SP-A content was determined by enzyme-linked immunosorbent assay using a polyclonal antibody raised against rat SP-A purified from lavage. Type II cells cultured on plastic dishes assumed an attenuated morphology soon after being placed in culture. Except for an occasional positive signal on day 2 of culture, these cells were uniformly negative for the presence of mRNA for SP-A, SP-B, or SP-C. Type II cells cultured on plastic did not contain SP-A. In contrast, type II cells cultured on EHS gels formed three-dimensional aggregates on the surface of the substratum; these aggregates were composed of polarized cells that had their apical surfaces directed inward. Type II cells cultured on this substratum showed a positive signal for mRNA for all three surfactant proteins; the abundance of these mRNAs, however, was significantly below that seen in freshly isolated type II cells. While the abundance of mRNA for SP-A and SP-B steadily increased with time in culture under these conditions, the abundance of SP-C mRNA decreased, suggesting that SP-C is regulated independently of SP-A and SP-B. These cultures were also positive for SP-A content, which increased with increasing time in culture. Type II cells cultured on laminin-coated dishes initially spread more slowly across the culture surface than cells on plastic, but were extremely attenuated by day 8 in culture. These cells contained neither SP-A, nor mRNA for any of the three surfactant proteins.(ABSTRACT TRUNCATED AT 400 WORDS)
Am J Respir Cell Mol Biol 1990 Feb
PMID:Effect of a reconstituted basement membrane on expression of surfactant apoproteins in cultured adult rat alveolar type II cells. 230 74

Because surfactant proteins A, B, and C (SP-A, SP-B, and SP-C) are putative markers for alveolar epithelial type II cells, we investigated their expression in embryonic rat lung (12 to 15 days, term = 22 days). The expression of the messages for SP-A, SP-B, and SP-C was assessed by the reverse-transcriptase polymerase chain reaction (RT-PCR). Embryonic rat lung at 12 days' gestation lacked detectable mRNAs for all three surfactant proteins. Messages for SP-A, SP-B, and SP-C were, however, present in embryonic rat lung at 13 days' gestation. Expression of SP-A mRNA increased in embryonic rat lung with advancing gestation. Surfactant protein mRNA expression during the embryonic period of lung development was limited to the epithelial cells. The expression of SP-A mRNA, while limited to the lung, did not appear to be a marker for cells destined to become type II cells, since it was detected in the trachea and the presumptive main bronchial ducts of embryonic rat lung at 13 days' gestation, as well as in the distal lung prealveolar region. Expression of both SP-B and SP-C mRNAs in embryonic lung was confined to the distal portion of the ductal system, although message of SP-C was also found in brain and kidney. These results suggest that none of the three surfactant protein mRNAs studied are, at this early stage of lung development, specific for cells destined to become type II pneumocytes.
Am J Respir Cell Mol Biol 1994 Feb
PMID:Expression of surfactant proteins in embryonic rat lung. 750 64

Retinoids have been shown to influence pattern formation during development and regeneration in numerous systems such as limbs, vertebrae, and neural tube although there is little information about the effects of retinoids on pattern formation in visceral organs. We investigated the effects of exogenous retinoic acid on the in vitro pattern of airway branching and on lung epithelial cell differentiation. Histology, [3H]thymidine autoradiographies and reverse transcriptase/polymerase chain reaction (RT/PCR) amplification were used to assess the effects of retinoids and the expression of lung epithelial markers of differentiation. We found that retinoic acid interferes, in a dose-dependent fashion, with the expression of epithelial genes that are found in distal segments of the fetal lung (surfactant-associated proteins SP-A, SP-B, and SP-C). At high concentrations, retinoic acid (RA) dramatically altered the developmental pattern of the lung, favoring growth of structures that resemble proximal airways and concomitantly suppressing distal epithelial buds. We hypothesize that this in vitro "proximalizing" effect on the developing lung may be related to alterations in the expression of pattern-related genes.
Am J Respir Cell Mol Biol 1995 May
PMID:Retinoic acid induces changes in the pattern of airway branching and alters epithelial cell differentiation in the developing lung in vitro. 774 11

The pulmonary surfactant lines as a complex monolayer of lipids and proteins the alveolar epithelial surface. The monolayer dynamically adapts the surface tension of this interface to the varying surface areas during inhalation and exhalation. Its presence in the alveoli is thus a prerequisite for a proper lung function. The lipid moiety represents about 90% of the surfactant and contains mainly dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol (PG). The surfactant proteins involved in the surface tension adaption are called SP-A, SP-B and SP-C. The aim of the present investigation is to analyse the properties of monolayer films made from pure SP-C and from mixtures of DPPC, DPPG and SP-C in order to mimic the surfactant monolayer with minimal compositional requirement. Pressure-area diagrams were taken. Ellipsometric measurements at the air-water interface of a Langmuir film balance allowed measurement of the changes in monolayer thickness upon compression. Isotherms of pure SP-C monolayers exhibit a plateau between 22 and 25 mN/m. A further plateau is reached at higher compression. Structures of the monolayer formed during compression are reversible during expansion. Together with ellipsometric data which show a stepwise increase in film thickness (coverage) during compression, we conclude that pure SP-C films rearrange reversibly into multilayers of homogenous thickness. Lipid monolayers collapse locally and irreversibly if films are compressed to approximately 0.4 nm2/molecule. In contrast, mixed DPPG/SP-C monolayers with less than 5 mol% protein collapse in a controlled and reversible way. The pressure-area diagrams exhibit a plateau at 20 mN/m, indicating partial demixing of SP-C and DPPG.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Membr Biol
PMID:Pulmonary surfactant protein C containing lipid films at the air-water interface as a model for the surface of lung alveoli. 776 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>