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1.
The biosynthesis of phosphatidylcholine was studied in a population of activated Type II cells isolated from the lungs of rats treated with silica. Type II cells were separated by centrifugal elutriation 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 cells; Type IIA cells were morphologically similar to normal Type II cells. Type IIB cells incorporated more [Me-14C]choline into both total phosphatidylcholine and disaturated phosphatidylcholine than did Type IIA or control Type II cells. Measurement of the pool sizes of the choline-containing precursors to phosphatidylcholine indicated that the biosynthesis of phosphatidylcholine was increased 4- to 5-fold in Type IIB cells. Increased conversion of cholinephosphate to CDP-choline was associated with increased phosphatidylcholine biosynthesis in Type IIB cells. Cholinephosphate cytidylyltransferase activity was increased approximately threefold in Type IIB cells. Subcellular fractionation indicated that essentially all of the increase in cytidylyltransferase activity was associated with the particulate fraction (100,000 x g pellet). In Type IIB cells, the particulate fraction contained 83% of the total cellular cytidylyltransferase activity; in control cells, this fraction contained 67% of the total activity. The specific activity of the cytidylyltransferase associated with the particulate fraction was increased twofold in Type IIB cells. The specific activity of the cytosolic enzyme was similar to that in control cells. Cholinephosphotransferase specific activity was increased approximately twofold in the activated Type II cells. The specific activity of choline kinase was the same as that in control Type II cells. These results demonstrate that the increased biosynthesis of phosphatidylcholine in Type IIB cells is a result of stimulation of the CDP-choline pathway. This study indicates that both cholinephosphate cytidylyltransferase and cholinephosphotransferase may be involved in regulating the de novo biosynthesis of phosphatidylcholine in alveolar Type II cells. 相似文献
2.
Silica-induced hypertrophy of type II cells in the lungs of rats 总被引:5,自引:0,他引:5
B E Miller L A Dethloff G E Hook 《Laboratory investigation; a journal of technical methods and pathology》1986,55(2):153-163
Several investigators have reported the appearance of hypertrophic type II cells in the lungs of silica-treated rats. The purpose of this study was to isolate and characterize these hypertrophic type II cells. Lungs were digested with trypsin and the released cells were separated by using a flow gradient during centrifugal elutriation. Type II cells from control lungs were distributed in the flow gradient as a single population, whereas type II cells from the lungs of silica-treated rats had a bimodal distribution suggesting the presence of two distinct populations of type II cells; one of these populations appeared hypertrophic (type IIB) and the other appeared normal (type II cells; one of these populations appeared hypertrophic (type IIB) and the other appeared normal (type IIA). These two populations of type II cells from silica-treated rats differed significantly in cell size and their lamellar body content. The mean volume of type IIA and type IIB cells was 350 +/- 38 micron 3 and 523 +/- 29 micron 3, respectively. The mean number of lamellar bodies in type IIA and type IIB cells was 77 +/- 53 and 131 +/- 84 per cell, respectively. The mean volume of lamellar bodies was 0.39 +/- 0.09 micron 3 in type IIA cells and 0.66 +/- 0.10 micron 3 in type IIB cells. Type IIA cells were not significantly different from type II cells from the lungs of untreated rats. The distribution of type II cells from silica-treated lungs was such that 2 weeks after a single intratracheal injection of silica (10 mg/rat) type IIB cells accounted for 39.2 +/- 6.4% of the total type II cells recovered after centrifugal elutriation. The general morphological appearance of the isolated type IIA and type IIB cells was similar to that observed in type II cells isolated from untreated rats. These data indicate that hypertrophic type II cells may be isolated from the lungs of silica-treated rats and separated from normal type II cells thus allowing the role of these unusual type II cells in lung injury and repair to be investigated. 相似文献
3.
Induction of surfactant protein (SP-A) biosynthesis and SP-A mRNA in activated type II cells during acute silicosis in rats 总被引:1,自引:0,他引:1
B E Miller W E Bakewell S L Katyal G Singh G E Hook 《American journal of respiratory cell and molecular biology》1990,3(3):217-226
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. 相似文献
4.
Temporal segregation of surfactant secretion and lamellar body biogenesis in primary cultures of rat alveolar type II cells 总被引:2,自引:0,他引:2
A Suwabe R J Mason D R Voelker 《American journal of respiratory cell and molecular biology》1991,5(1):80-86
Pulmonary alveolar type II cells synthesize and secrete the phospholipids of surfactant. However, type II cells isolated from adult rat lungs rapidly lose their characteristic morphology and differentiated functions (such as surfactant-specific phospholipid and protein biosynthesis) when maintained on tissue culture plastic. In this study, phospholipid secretion and its regulation by type II cells grown on tissue culture plastic were examined up to 8 days after isolation. Type II cells were preincubated with [3H]choline for varying 24-h periods during culture prior to examining phosphatidylcholine ([3H]PtdCho) secretion. Type II cells cultured for 4 days and incubated with [3H]choline 24 h before the secretion experiment failed to show significant basal and tetradecanoyl phorbol acetate (TPA, 100 nM)-stimulated [3H]PtdCho secretion (basal, 0.29 +/- 0.01%; TPA, 0.48 +/- 0.04%). In contrast, type II cells incubated with [3H]choline for the first 24 h during culture and then cultured for 3 more days showed significant [3H]PtdCho secretion (basal, 1.27 +/- 0.19%; TPA, 6.24 +/- 0.82%). Subcellular fractionation of type II cells revealed that [3H]choline was incorporated into phosphatidylcholines in a lamellar body-enriched fraction during the first 24 h of culture but that the assimilation of phosphatidylcholine into the lamellar body fraction progressively declined with increasing time in culture. Radiolabel incorporated into the lamellar body fraction labeled during the first 24 h of culture was detectable for up to 8 days in culture. The [3H]PtdCho incorporated into the lamellar body during the first 24 h of culture was lost gradually over 8 days, suggesting the continuous secretion or turnover of the lamellar bodies during culture.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
5.
Effects of oxygen metabolites on rat alveolar type II cell viability and surfactant metabolism 总被引:1,自引:0,他引:1
C Crim R H Simon 《Laboratory investigation; a journal of technical methods and pathology》1988,58(4):428-437
Neutrophil-derived reactive oxygen metabolites have been implicated as one mechanism for the cellular injury in the adult respiratory distress syndrome. Previous studies have demonstrated that alveolar lung fluid of patients with adult respiratory distress syndrome has abnormal composition and surface active properties. To examine the effects of oxygen metabolites on the viability and metabolism of type II alveolar pneumocytes, the cellular source of surfactant, isolated rat type II pneumocytes were exposed to reactive oxygen metabolites generated by the enzymatic action of xanthine oxidase upon hypoxanthine. Utilizing a 51Cr release assay to detect cellular death, we found that oxygen metabolites were lethal to type II cells in a dose-dependent manner. To demonstrate that oxygen metabolites were responsible for the toxicity, we assessed the protective effects of catalase and superoxide dismutase, scavengers of hydrogen peroxide and the superoxide anion, respectively. At a xanthine oxidase concentration of 50 mU/ml, catalase reduced the percentage of 51Cr release from 58.9 +/- 3.1% (SEM) to 7.2 +/- 2.3% (p less than 0.0001), whereas superoxide dismutase was without protection (58.9 +/- 3.1% versus 54.2 +/- 1.8% (p greater than 0.05). To determine whether oxygen metabolites also impair surfactant metabolism, we measured the incorporation of [3H]palmitate into the surfactant component disaturated phosphatidylcholine by type II pneumocytes. We found that sublethal amounts of generated oxygen metabolites caused a progressive decrease in the amount of [3H]palmitate incorporated into disaturated phosphatidylcholine. For example, using a xanthine oxidase concentration of 5 mU/ml (which causes no increased 51Cr release), we found that [3H]palmitate incorporation into disaturated phosphatidylcholine fell from a control level of 3.53 +/- 0.22 X 10(5) to 0.66 +/- 0.10 X 10(5) dpm/10(6) cells/4 hours (p less than 0.0001). Both catalase and superoxide dismutase protected the [3H]palmitate incorporation of oxygen metabolite-exposed type II cells. We conclude that reactive oxygen metabolites are injurious to type II pneumocytes and may result in impaired surfactant synthesis even at sublethal doses. Thus, oxygen metabolites generated by stimulated phagocytic cells may be responsible in part for the decreased surfactant that has been observed in adult respiratory distress syndrome. 相似文献
6.
The type II epithelial cells of the lung. III. Lecithin synthesis: a comparison with pulmonary macrophages 总被引:1,自引:0,他引:1
F B Smith Y Kikkawa 《Laboratory investigation; a journal of technical methods and pathology》1978,38(1):45-51
Synthesis of lecithins in isolated type II alveolar cells was compared with that in alveolar macrophages as a means of exploring the biochemical mechanisms underlying surfactant production in the lung. Counted cell populations were suspended in a simple glucose-salt solution and 14C-labeled precursors were added singly, in physiologic concentrations, to assess the potential importance of each as a substrate for lecithin synthesis. Molar incorporation of glucose, glycerol, choline, lysolecithin, acetate, palmitate, oleate, and linoleate was determined in lecithins fractionated according to degree of saturation after 1 hour of incubation. Palmitate ws the most actively utilized substrate in type II &cells. Type II cells incorporated 6 nmoles of palmitate per 10(7) cells, of which 77% was in disaturated lecithins, and 66% at the C2 position (compared to 0.8 nmoles, 47% disaturated, in macrophages). Acetate was also incorporated mainly into disaturated lecithins in type II cells; macrophages did not utilize acetate, and no precursor specifically supported disaturated lecithin synthesis in macrophages. Type II cells and macrophages synthesized similar quantities of total lecithins and disaturated lecithins from glucose and choline. Only the type II cells, however, were capable of increasing disaturated lecithin synthesis from 14C-choline when unlabeled palmitate was added to the medium. Type II cells synthesized significantly more disaturated lecithins from lysolecithin than did macrophages (451 versus 60 pmoles per 10(7) cells). Macrophages utilized glycerol in lecithin synthesis, but type II cells did not. Our data demonstrate directly for the first time that type II cells are the site of disaturated lecithin synthesis and that acyl turnover mechanisms are important in production of disaturated lecithins by the type II cell. 相似文献
7.
A Suwabe R J Panos D R Voelker 《American journal of respiratory cell and molecular biology》1991,4(3):264-272
We examined surfactant secretion and its regulation by surfactant protein A (SP-A) in alveolar type II cells isolated from silica-treated rats to determine the role of SP-A-mediated regulatory control of phospholipid secretion in the pathogenesis of silica-induced alveolar proteinosis. Type II cells were isolated at weekly intervals for 28 d after silica or saline instillation. The maximum total binding of [125I]SP-A (internalized and surface-bound SP-A) to type II cells increased with time after silica instillation and, at 21 d, was 4-fold greater than that of type II cells isolated from saline-treated rats (272.8 +/- 42.5 and 65.4 +/- 9.8 ng/10(5) cells, respectively; P less than 0.05). Type II cells isolated from silica-treated rats showed a 2-fold increased surface binding and a 3-fold increased internalization compared to control cells. The receptor affinity for SP-A was the same for type II cells isolated from silica- and saline-treated animals. Type II cells isolated 14 d after silica instillation were separated into normotrophic and hypertrophic populations by centrifugal elutriation. Hypertrophic cells showed significantly elevated maximum total binding compared to normotrophic cells. The secretion of [3H]phosphatidylcholine [( 3H]PC) by type II cells from silica- and saline-treated animals was also compared. Type II cells from silica-treated animals showed lower basal and tetradecanoyl phorbol acetate (TPA)-stimulated [3H]PC secretion than cells from saline-treated animals at each time point after instillation. SP-A inhibited TPA-stimulated [3H]PC secretion similarly in type II cells isolated after either silica or saline instillation.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
R M Viscardi S Ullsperger M C McKenna 《Laboratory investigation; a journal of technical methods and pathology》1991,65(2):250-257
Carbon stripping is a process that is widely used to remove hormones from serum. Because addition of serum to culture media also provides exogenous fatty acids that influence lipid metabolism of cultured cells, we investigated the effects of carbon stripping on the composition of the phospholipid and free fatty acid fractions in fetal bovine serum and the effects of these changes on phosphatidylcholine synthesis by cultured adult alveolar type II cells. Carbon stripping resulted in quantitative and qualitative changes in serum free fatty acids. The process effectively extracted greater than or equal to 99% free fatty acids and, to a lesser extent, phospholipids. There were also qualitative changes in the relative composition of the remaining free fatty acids with a selective loss of oleic and linoleic free fatty acids. However, the relative composition of the serum phospholipid fatty acid fraction was unaffected. Type II cells isolated from adult male rat lung and cultured in Dulbecco's modified Eagle's medium supplemented with 10% carbon-stripped fetal bovine serum (FBS-CS) incorporated [3H]choline into phosphatidylcholine at a rate 36% less than the rate of control cells cultured with unstripped FBS. Addition of oleic acid to FBS-CS supplemented media increased total phosphatidylcholine synthesis by adult type II cells by 67-71%. In contrast, addition of palmitic acid inhibited PC synthesis 51-67%. The combination of oleic and palmitic acids resulted in a rate of [3H]choline incorporation into phosphatidylcholine similar to the rate for control cells cultured in FBS-CS-supplemented media alone. Although synthesis of disaturated phosphatidylcholine was unaffected by exogenous fatty acids, addition of fatty acids altered the proportion of disaturated phosphatidylcholine synthesis relative to total phosphatidylcholine synthesis. The presence or absence of the hormones, dexamethasone and triiodothyronine, did not explain the difference in rate of phospholipid synthesis by type II cells cultured in untreated versus carbon-stripped serum supplemented media. These results suggest that the removal of serum free fatty acids by carbon stripping can influence phospholipid metabolism of cultured type II cells. Because serum free fatty acids influence cellular lipid composition and potentially cell metabolic functions, carbon-stripped serum may not be the optimal choice for media supplementation of cultured cells. 相似文献
9.
Progression of type II cell hypertrophy and hyperplasia during silica-induced pulmonary inflammation 总被引:4,自引:0,他引:4
B E Miller L A Dethloff B C Gladen G E Hook 《Laboratory investigation; a journal of technical methods and pathology》1987,57(5):546-554
Type II cell hyperplasia and hypertrophy were quantitated in the lungs of rats exposed to silica by using intratracheal injection. Hypertrophic type II cells were separated from normal type II cells by means of centrifugal elutriation of cells dispersed from the lungs by using protease. Type II cell hypertrophy was also quantitated, in situ, by measuring cell profile areas in lung sections. As a means of distinguishing between the hyperplastic and hypertrophic responses of type II cells we followed the progression of these two responses as a function of time and of dose. Seven, 14, and 28 days after a single intratracheal injection of silica (10 mg/rat), hypertrophic type II cells accounted for 33, 35, and 57% of the total type II cells recovered from the lungs. In contrast, hypertrophic type II cells accounted for less than 15% of the type II cells from control lungs. The appearance of hypertrophic type II cells was dose-related when examined 2 weeks after dosing; however, after only 1 week, the response of the type II cell appeared independent of dose. The hypertrophic response of type II cells could not be separated from the hyperplastic response according to either dose or time responses. These data support the hypothesis that in the lungs of silica-treated rats, the hypertrophic type II cell may be the proliferative type II cell. In addition, the hypertrophic type II cell appears to underlie the marked increases in surfactant levels seen in silica-treated lungs. 相似文献
10.
Hypertrophic alveolar type II cells from silica-treated rats are committed to DNA synthesis in vitro 总被引:4,自引:0,他引:4
R J Panos A Suwabe C C Leslie R J Mason 《American journal of respiratory cell and molecular biology》1990,3(1):51-59
Alveolar type II cell hyperplasia and hypertrophy are common reparative responses of the alveolar epithelium after silica-induced lung injury. We studied in vitro DNA synthesis in type II cells isolated after silica instillation in the rat to determine the proliferative potential of silica type II cells in primary culture and to correlate alveolar type II cell size with the level of in vitro DNA synthesis. To determine if the alveolar lining fluid is a source of growth factors that stimulate alveolar type II cell proliferation, we also examined the mitogenic effect of bronchoalveolar lavage fluid (BALF) from silica-treated rats on type II cells in primary culture. Alveolar type II cells were isolated from rats 1, 2, 3, and 4 wk after intratracheal silica instillation, cultured in DME supplemented with 10% fetal bovine serum, and labeled with [3H]thymidine from day 1 to day 3 in culture. DNA synthesis was determined by [3H]thymidine incorporation and autoradiographic labeling index. The level of thymidine incorporation increased progressively from 22.3 +/- 5.4 x 10(3) dpm/well 7 d after silica instillation to 34.4 +/- 5.0 x 10(3) dpm/well at 28 d. Type II cells isolated 14 d after silica instillation were separated into groups of increasing cell size by centrifugal elutriation. The plating efficiency and alveolar type II cell purity (greater than 88%) were the same in all groups of elutriated cells. The hypertrophic type II cells had a higher level of thymidine incorporation (22.0 +/- 2.8 x 10(3) dpm/well) than the normotrophic type II cells (11.1 +/- 0.7 x 10(3) dpm/well) [P less than 0.01]).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
11.
Lecithin biosynthesis in a clonal line of lung adenoma cells with type II alveolar cell properties 总被引:1,自引:0,他引:1
The content and synthesis of certain phospholipids associated with lung surfactant has been investigated in a clonal line of epithelial cells derived from mouse lung adenoma. These cells, designated LA-4, possess osmiophilic intracytoplasmic lamellar inclusion bodies similar in appearance to lamellar bodies observed in normal type 2 alveolar epithelial cells (Stoner et al., 1975).Lecithin was the most abundant phospholipid in the LA-4 cells, comprising more than 50% of all phospholipid. LA-4 cells had significantly higher contents of total lecithin than in vivo adenoma and normal lung, but a lower proportion (27–29%) of the total lecithin in disaturated form than normal lung (36%). In addition, LA-4 cells had a significantly higher proportion of total lecithin in disaturated form than a clonal line of mouse lung fibroblasts (14%). The content of phosphatidylglycerol in LA-4 cells was significantly lower than in normal lung.Radiolabeled precursor studies showed that palmitic acid was rapidly incorporated into disaturated lecithin of LA-4 adenoma cells and to a greater extent than glycerol, suggesting that the saturation pathways forming disaturated lecithins are active. Studies with radiolabeled choline and methionine suggest that LA-4 cells synthesize total and disaturated lecithins de novo principally through the choline incorporation pathway, with a minor contribution by the three-step methylation of phosphatidyl-ethanolamine.The present results indicate that the phospholipid metabolism of lung adenoma cells is preserved when cultured in vitro. Urethan-induced transformation of type 2 alveolar cells appears to result in a diminished capacity of the cells to synthesize phosphatidylglycerol and disaturated phosphatidylcholine. 相似文献
12.
Epidermal growth factor (EGF) increases the rate of choline incorporation into disaturated phosphatidylcholine in cultured fetal rat type II cells via an indirect mechanism. Whereas-EGF has no effect on the rate of disaturated phosphatidylcholine synthesis when added directly to type II pneumocytes, the growth factor is effective if it is present during preliminary conditioning of the media by lung fibroblasts. This effect is concentration dependent with a maximal effect at 20 ng/ml. When lung fibroblasts are incubated with both glucocorticoids and EGF, there is no significant effect of the growth factor over and above that seen with the steroid alone. This suggests that the two agents might act via a similar mechanism. This is supported by the observation that each inducer leads to the production by lung fibroblasts of a stimulatory factor that has a similar, if not identical, chromatographic elution profile. We conclude that EGF may contribute significantly to the normal onset of lung maturation by elaborating a fibroblast-derived factor that stimulates phosphatidylcholine synthesis in type II pneumocytes. 相似文献
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15.
Summary A differential plating method permitted preparation of cultures significantly enriched for Type II pneumocytes. These cells were maintained in a differentiated state for at least 12 d, identifiable morphologically (by presence of osmiophilic lamellar inclusion bodies) and bio-chemically (by demonstration of synthesis of phosphatidyl choline and production of disaturated lecithin). 相似文献
16.
Iprindole reverses the lamellar body deficiency of cultured L-2 cells. Possible implications in the reversal of surfactant deficiency.
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Type II alveolar epithelial cells in long-term culture typically lose the ability to synthesize surfactant together with a loss of the characteristic lamellar bodies in the cytoplasm of the cells. Iprindole, a cationic amphiphilic drug, induces lamellar body formation in cultured L-2 cells, a cell line derived from rat Type II cells, but devoid of lamellar bodies. With concentrations of 10(-7)-10(-5) M iprindole, which approximate therapeutic plasma concentrations in human subjects, the drug induced the formation of lamellar bodies within 8 hours of incubation. This effect on cell morphology was rapidly lost after withdrawal of the drug. At concentrations of iprindole which induced lamellar body formation, there was a significant increase in phospholipid content of the L-2 cells as well as an increase in disaturated phosphatidylcholine, an important constituent of surfactant. These studies suggest that the use of drugs such as iprindole may represent a novel approach in the augmentation of phospholipid (and possibly surfactant) content of Type II cells in the lung. 相似文献
17.
R J Panos N F Voelkel G R Cott R J Mason J Y Westcott 《American journal of respiratory cell and molecular biology》1992,6(4):430-438
Although alveolar type II cells in primary culture have been shown to produce eicosanoids and exposure of type II cells to silica in vitro alters eicosanoid production, the production of eicosanoids by alveolar type II cells isolated after acute lung injury in vivo has not been evaluated. Therefore, we investigated the production of arachidonic acid (AA) metabolites by alveolar type II cells isolated after silica-induced lung injury. Alveolar type II cells were isolated from rats 14 days after intratracheal silica instillation and from untreated animals. Type II cells were separated into normotrophic and hypertrophic populations by centrifugal elutriation, and secreted eicosanoids were determined under basal and stimulated conditions by enzyme immunoassay on the day of isolation and after 1 day in culture. Under basal conditions, freshly isolated type II cells from silica-treated animals produced more prostaglandin (PG) E2 than 6-keto-PGF1 alpha or thromboxane B2 (TxB2). Production of all three prostanoids increased with increasing cell size. The calcium ionophore A23187 stimulated a less than 2-fold increase in PGE2 and 6-keto-PGF1 alpha production in all groups of cells. In contrast, this calcium ionophore greatly enhanced TxB2 and leukotriene C4 (LTC4) production by normotrophic type II cells from both untreated and silica-treated animals. Incubation with exogenous AA suggested that the increased capability of the hypertrophic cells to synthesize PGE2 and TxB2 was due primarily to an increase in arachidonate availability. The hypertrophic type II cells also appear to have increased prostacyclin synthase activity. There were no differences in the catabolism of PGE2 between the normotrophic and the hypertrophic type II cells.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
18.
Gewolb IH O'Brien J Slavin RE 《American journal of respiratory cell and molecular biology》1999,20(3):511-516
Infants born to heroin- and cocaine-addicted mothers have been reported to have a lower incidence of respiratory distress syndrome (RDS) compared with nonaddicted infants. However, it is not known whether these are direct drug-mediated effects or secondary phenomena. We therefore investigated the effect of opioids and cocaine on fetal rat lung maturation in vitro. Using 18- to 20-d fetal rat lung explants and 20-d fetal type II cells, we measured the effect of varying concentrations (1 x 10(-8) to 1 x 10(-3) M) of heroin, morphine, methadone, and the nonopioid cocaine on the rate of choline incorporation into phosphatidylcholine (PC) and disaturated PC. We also analyzed the morphology of 19-d explants after exposure to opioids. Significant increases in rate of choline incorporation were noted in 19- and 20-d explants using 1 x 10(-3) M heroin, 1 x 10(-3) M morphine, and 1 x 10(-4) M methadone (P < 0. 005). No acceleratory effect was seen with cocaine. Morphologic analysis of the three opioid-treated groups revealed a significant (192 to 251%) increase in type II pneumocytes and lamellar bodies per alveolar lining cell (P < 0.01). Choline incorporation into PC by type II cells was also significantly increased by opioids (P < 0. 01); lactate dehydrogenase release and cell viability were not affected by opioid treatment. These data indicate that high-dose opioids have an acceleratory effect on biochemical and morphologic parameters of fetal lung maturation in vitro. The lack of in vitro acceleration with cocaine suggests that any cocaine-related reduction in the incidence of RDS is a secondary effect. 相似文献
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20.
Phospholipid profile of Pneumocystis carinii and its interaction with alveolar type II epithelial cells. 总被引:5,自引:0,他引:5
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E L Pesanti 《Infection and immunity》1987,55(3):736-741
Pneumocystis carinii is an obligate parasite of mammalian lungs, attaching to but not invading the alveolar epithelium. The alveolar air spaces are rich in phospholipids, which are secreted by steroid-responsive alveolar type II epithelial cells. P. carinii isolated from rat lungs was found to contain the expected structural phospholipids as well as a large amount of firmly attached disaturated phosphatidylcholine, the characteristic phospholipid of alveolar surfactant. In vitro, P. carinii cells synthesized phospholipids from simple radiolabeled precursors; disaturated phosphatidylcholine was not formed. However, washed P. carinii cells avidly adsorbed radiolabeled rat surfactant, a process that appeared to be saturable, not dependent on viability of the organisms, and abolished by incubation at 4 degrees C. The surfactant was neither harmful nor beneficial to in vitro survival of the organisms. With the exception of high concentrations of arachidonic acid, fatty acids found in rat alveolar lining material were also not toxic. In addition, cultures consisting primarily of rat type II alveolar epithelial cells were toxic to P. carinii when the organisms were added to monolayers of type II cells at less than or equal to 10:1 multiplicity. At higher multiplicities, the parasite survived (but did not increase in numbers), and the type II cells deteriorated. The mechanism for this effect has not been determined. 相似文献