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Departments of 1Pediatric Pulmonology and Neonatology and 3Applied and Functional Anatomy, Hannover Medical School, 30625 Hannover; 4Solvay Pharmaceuticals GmbH, 30173 Hannover, Germany; and 2Child Health, University of Southampton, Southampton SO16 6YD, United Kingdom
Submitted 3 December 2001 ; accepted in final form 4 May 2002
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ABSTRACT |
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 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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airway surfactant; lung surfactant; molecular species; phosphatidylcholine synthesis; mass spectrometry
/r,
where P is pressure, is surface tension, and r is alveolar
radius). Other PL, namely, phosphatidylglycerols and PC species with short and
monounsaturated fatty acid chains, are less rigid, spread readily on the
surface, and enable replenishment of the surfactant film during inspiration.
These properties meet the requirement of the alveolar environment with its
uniquely high surface area-to-volume ratio coupled with rapid, dynamic area
change during the breathing cycle.
Small airways have a similarly high surface area-to-volume ratio, and,
according to the law of Laplace as it applies for tubules (P =
/r, where P is opening pressure, is surface tension,
and r is radius of the tubule), one would expect high surface
tension, leading to influx of fluid or collapse of the tubule, which is not
seen in healthy animals and humans. This has led to the postulation of the
importance of surfactant in stabilizing small airways
(20,
21). In agreement with this,
an essential role of surfactant for airway function was recently highlighted
by the finding of impaired function and altered PL composition of surfactant
from sputum of asthmatic patients after local allergen challenge
(27,
48). Additionally, surfactant
may contribute to airway function by improving mucociliary transport because
of its antiglue properties and by suppression of bronchial irritant receptors
(2,
27,
33). The secretions in the
conducting airways of healthy humans and animals contain significant amounts
of PL with a composition almost identical to that of alveolar surfactant
(7,
38,
48). Consequently, it was
suggested that these PL originate from the alveolar type II pneumocytes, and
in some studies, airway aspirations were used to investigate maturation of the
alveolar surfactant system (3,
8,
38). Because, under
pathological conditions, impaired surface tension function in the airways was
associated with altered PL composition
(24,
46,
48), knowledge of the origin
of airway PL is essential to assess the contribution of the underlying tissue.
Under physiological conditions, the presence of surfactant PL in airways can
be explained by leakage from the alveolar spaces
(26), whereas, under
pathological conditions, altered surface tension function and PL composition
of airway fluids can be explained by contaminations from desquamated or
invaded cells or by the influx of blood plasma proteins and PL due to barrier
dysfunction (24,
44,
48). Nevertheless, secretion
of surfactant-like PL by airway mucosa and mucosal surfaces of other organs
has been suggested (13,
17,
19,
22,
25,
33,
47). To rule out any
contribution of the underlying tissue to the surfactant fraction in airway
secretions (7,
13,
25,
47), we investigated the
composition, synthesis, and secretion of PC molecular species in the rat
trachea compared with the lungs. We used
[methyl-3H]choline as a precursor for labeling experiments
with isolated tracheae and lungs and HPLC as well as electrospray ionization
mass spectrometry (ESI-MS) for identification of individual PC molecular
species of the respective tissues and their secretions. This study aimed to
discriminate between the composition of PC molecular species synthesized in
and released from airway mucosa and the composition of PC molecular species in
the airway surfactant originating from the alveolus.
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MATERIALS AND METHODS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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3 h, was
performed with minor variations as described elsewhere
(25). The metabolic integrity
of the organ cultures was verified by constant rates of
[methyl-3H]choline incorporation into tissue PL throughout
the experimental period, which was previously demonstrated in similar in vitro
experiments showing linear incorporation of labeled choline over 6-24 h
(12,
39).
[Methyl-3H]choline was used as a precursor, because it is
an essential nutrient for extrahepatic tissues and is incorporated into all PC
molecular species according to their fractional synthesis rates
(5,
37,
49). Initial
[methyl-3H]choline incorporation represents de novo
synthesis of PC molecular species via the Kennedy pathway. By contrast,
subsequent deacylationreacylation processes (acyl remodeling mechanism) start
within 3 h after initial de novo synthesis of PC and result in shifts of the
[methyl-3H]choline label among individual PC species. In
lungs, such secondary acyl remodeling leads to a selective accumulation of
PC16:0/16:0 at the expense of unsaturated PC species. Consequently, fractional
[methyl-3H]choline labeling of PC16:0/16:0 is initially
lower than the molar fraction of PC16:0/16:0 in relation to total PC, whereas
at later time points the fractional label is equal to its molar fraction
(5,
6). By contrast, in tissues
that do not secrete PL with a composition similar to that of lung surfactant,
such as stomach mucosa (32),
the small amounts of newly synthesized PC16:0/16:0 are quickly degraded,
rather than accumulated
(43). Briefly, specific pathogen-free Sprague-Dawley rats (160-200 g body wt) from our local animal facilities were fed regular rodent chow and tap water until death. All animals were housed, cared for, and killed in accordance with the recommendations of the European Commission. The Animal Ethics Committee of the State of Lower Saxony, Germany, approved all experimental protocols. Animals were anesthetized with pentobarbital sodium (60 mg/kg body wt ip; Nembutal, Sanofi cefa, Hannover, Germany), to which heparin sodium (1,000 IU; Hoffmann-LaRoche, Basel, Switzerland) was added to prevent intravascular coagulation. For isolation of the trachea, the neck and thorax of the animal were opened. The trachea was fixed with a thin thread at the cranial end and excised from below the larynx to the bifurcation of the stem bronchi. The trachea was then transferred to a culture dish with ice-cold medium, and both ends were connected to the stainless steel tips of two 2 x 1-mm silicone tubes, which were connected to a 5-ml reservoir of RPMI-1640 medium (Sigma, Steinheim, Germany) for superfusion from the luminal side at a flow rate of 0.5 ml/min. Care was taken to remove adherent structures of muscle or connective tissue. The isolated trachea was then placed in an isolated and tempered glass chamber filled with 15 ml of RPMI-1640 medium (37°C, pH 7.35-7.40). The isolation procedure lasted <10 min. The medium in the reservoir and culture chamber was equilibrated with water-saturated 95% oxygen-5% carbon dioxide throughout the experiment. Total choline concentration of the medium was 22 µmol/l. At 15 min after the start of the experiments, 92.5 kBq of [methyl-3H]choline (2.6 TBq/mmol specific activity; Amersham-Buchler, Braunschweig, Germany) were added to the luminal superfusion medium (5 ml), and 277.5 kBq were added to the medium in the culture chamber (15 ml). This did not significantly change final concentrations of choline and resulted in specific activity of 841 kBq/µmol on the luminal and adventitial sides. The higher labeling of tracheal (370 kBq/20 ml) than of lung culture medium (370 kBq/100 ml, 148 kBq/µmol, see below) was chosen to facilitate liquid scintillation counting of HPLC fractions from rat tracheal PC species, because the tracheae contained only 4-5% of the PL compared with rat lungs (see RESULTS). Perfusion experiments for electron microscopy were performed in the absence of radiolabel; all other experimental conditions were identical.
For lung perfusion, the trachea was cannulated with a 1.6 x 35-mm stainless steel catheter, and the lung was ventilated with a water-saturated mixture of 95% air-5% carbon dioxide (frequency = 12 strokes/min, peak inspiratory pressure = 10 cmH2O, end-expiratory pressure = 3 cmH2O) using a rodent ventilator (model 683, Harvard Apparatus, South Natick, MA). The thorax was opened, the pulmonary artery was catheterized with a section of 2 x 1-mm silicone tubing with a stainless steel tip, and the perfusion was started. Thirty milliliters of perfusion medium were used to clear the lung vasculature from blood and discarded. The lung was then positioned in a 37°C humidified chamber and perfused at a rate of 7-8 ml/min for 3.15 h with 100 ml of recirculating Krebs-Ringer-bicarbonate solution (37°C, pH 7.35-7.40). This perfusate, which contained 5% bovine serum albumin (fraction V, >96% purity; Sigma) and 5.6 mmol/l glucose, was gassed with a humidified mixture of 95% oxygen-5% carbon dioxide (9). After 15 min, choline chloride (2.5 µmol) supplemented with [methyl-3H]choline (370 kBq) was added to the perfusate, which was equivalent to 25 µmol/l choline and a specific activity of 148 kBq/µmol.
Electron microscopy of isolated tracheae. Tissue samples of
tracheae perfused for 3 h in the organ culture system were cut into thin
(
0.5-mm-thick) rings and immediately fixed in a solution containing 2%
formaldehyde and 2 mg/ml CaCl2 in 0.1 mol/l sodium cacodylate-HCl
buffer, pH 7.3. After they were dehydrated in ethanol dilutions and embedded
in Epon (Serva, Heidelberg, Germany), ultrathin 40- to 60-nm-thick sections
were stained with uranium acetate and lead citrate and examined in an electron
microscope (model EM 10, Zeiss, Oberkochen, Germany). Tissue samples
immediately removed after death served as controls.
Harvesting of tissue and tissue secretions. To harvest tracheal secretions, we collected the medium of the mucosal side and lung surfactant by bronchoalveolar lavage (BAL) with four 8-ml fractions of ice-cold saline 3 h after addition of [methyl-3H]choline to the medium. The respective secretions were then centrifuged for 10 min at 200 g and 4°C for removal of the cells (6). Medium containing tracheal secretions, BAL fluid (BALF), tracheal tissue, and lavaged lung parenchyma was then frozen in dry ice and stored at -80°C until analysis.
Extraction of PL and preparation of PC. Tissue samples were extracted following the procedure of Folch et al. (23), and medium and BALF were extracted according to the method of Bligh and Dyer (14). Inasmuch as the amount of PL from tracheal secretions was too low for PC preparation by solid-phase extraction and HPLC analyses, 1 µmol of PL from rat lung extract was added to the samples as a carrier before extraction (9). Extracts were then evaporated under a stream of nitrogen and adjusted to a defined volume with chloroform-methanol (7:3 vol/vol). PL phosphorus was quantified from sample aliquots as described by Bartlett et al. (4) after evaporation of the organic solvents and digestion of the organic compounds. Total PC, together with sphingomyelin, was prepared from sample aliquots (1 µmol of PL) by solid-phase extraction as previously described (40).
Analysis of PC molecular species with HPLC and ESI-MS. Individual PC molecular species were separated by reverse-phase HPLC on a 4.6 x 250 mm Sphere Image ODS II column (Schambeck, Bad Godesberg, Germany). HPLC effluents were derivatized by postcolumn fluorescence derivative formation in the presence of 1,6-diphenyl-1,3,5-hexatriene, and individual PC peaks were detected by fluorescence (excitation at 460 nm, emission at 340 nm) (40). For quantitation of [methyl-3H]choline incorporation, individual peaks were collected, and their 3H radiolabel was measured in a liquid scintillation analyzer (model 2000 CA TriCarb, Packard, Groningen, The Netherlands). Organic solvents were evaporated before the addition of scintillation cocktail (Luma-Safe Plus, Lumac*LCS, Groningen, The Netherlands). Counting efficiency was 33% for HPLC effluents, 41% for evaporated organic extracts, and 36% for 200-µl perfusate aliquots as determined by external tritiated standards.
ESI-MS analysis of PC species was performed using a single-quadrupole liquid chromatography mass spectrometer (API I, Perkin Elmer-Sciex, Toronto, ON, Canada) equipped with an electrospray ionization interface as described elsewhere (42). Briefly, PC preparations of rat trachea and lung extracts were dissolved in 100 µl of chloroform-methanol (1:2 vol/vol), and 5 µlof1 µmol/l sodium acetate in methanol were added to the samples directly before analysis. Samples were infused into the mass spectrometer via a syringe pump (model 22, Harvard Apparatus) at a flow rate of 3 µl/min. Dry heated nitrogen gas was used as the cone gas (60 l/h) and the dissolvation gas (60 l/h with a pressure of 40 psi). Samples were analyzed in the positive ionization mode, and data were recorded at atomic resolution as their sodium adducts (M + 22), with a signal average of 20 scans per collection. Data were processed using BioMultiview software (Perkin Elmer-Sciex). After correction for 13C isotope effects, molecular species of PC were expressed as percentages of total PC in the sample.
Statistics. Values are means ± SD. One-way analyses of variance were calculated using GraphPad Instat version 1.11a (GraphPad Software, San Diego, CA). Group differences were tested by a two-tailed Student's t-test using Bonferroni's correction for multiple group comparison, with P < 0.05 being considered significant.
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RESULTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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Comparative analyses with ESI-MS (Figs. 1B and 3) confirmed and extended these results, showing only minor contributions of PC16:0/16:0 to tracheal PC, whereas this was the major component in lung tissue. Additionally, ESI-MS analysis revealed that alkylacyl species of PC, which are not abundant in alveolar surfactant, comprised 14.5 ± 4.1% of total PC for rat trachea but only 8.0 ± 0.7% for rat lung parenchyma (P < 0.001). Additionally, compared with lung parenchyma, rat trachea contained significant amounts of PC species that were not detected by HPLC analysis, such as palmitoyldocosahexaenoyl-PC (PC 16:0/22:6, 1.14 ± 0.1 and 4.4 ± 0.4%, respectively, P < 0.001) and oleoylarachidonoyl-PC (PC 18:1/20:4, 1.6 ± 0.2 and 4.0 ± 0.2%, respectively, P < 0.001; Fig. 3). These PC species, together with the alkylacyl species, contributed to the large amount of unidentified PC peaks in HPLC analysis (Fig. 2).
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Electron microscopy of isolated trachea. To investigate synthesis and secretion of individual PC species by trachea compared with lung parenchyma, we performed labeling experiments with [methyl-3H]choline. Electron microscopy of tissue samples that were superfused for 3 h and controls, which were not superfused and directly fixed after removal, revealed that the integrity of cell and tissue structures in the epithelial and subepithelial layers was well preserved (Fig. 4). Compared with controls, only a small number of epithelial cells, mostly ciliated cells, showed decent swellings in their basal cytoplasm after perfusion.
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Synthesis of PC molecular species in isolated trachea and lung. Analysis of lipid-bound [methyl-3H]choline revealed that incorporation was linear over the whole period of labeling experiments (Fig. 5A). When we corrected for the incorporation rate of the fivefold-higher specific labeling of the tracheal superfusion medium than the lung perfusion medium (see MATERIALS AND METHODS) and of the amount of PL material, PC synthesis was substantially lower in tracheal than in lung tissue (Fig. 5B). Analyses of [methyl-3H]choline incorporation into the major individual PC species of tissues (Fig. 6A) revealed patterns of fractional synthesis similar to those of molecular composition in the isolated trachea and lung. However, although after 3 h 28.4 ± 1.9% of lipid-associated [methyl-3H]choline label was incorporated into PC16:0/16:0 of lung tissue, only 10.6 ± 0.3% was incorporated into PC16:0/16:0 of the trachea (P < 0.001; Fig. 6A). Similarly, for PC16:0/14:0 and PC16:0/16:1, the fractions of label were much lower in the trachea than in lung tissue (P < 0.001 each). In contrast to lung tissue, high proportions of label were found in PC16:0/18:2 and PC16:0/20:4 of rat trachea. Identical values of fractional [methyl-3H]choline incorporation were measured for other unsaturated PC species and ranged from 4% for PC18:0/18:2 and PC18:0/20:4 to 20% for PC16:0/18:1. The fractional label of PC16:0/16:0 in isolated trachea decreased from 13.1 ± 0.4% after 1.5 h to 10.6 ± 0.3% after 3 h (P < 0.0001), indicating degradation of PC16:0/16:0 after initial de novo synthesis. Interestingly, >20% of the [methyl-3H]choline label in rat trachea was found in those PC species that were only minor components in lung tissue, such as PC18:1/18:1, PC18:1/18:2, and several peaks that might contain the additional components only identified with ESI-MS (Fig. 1).
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Secretion of [methyl-3H]choline-labeled PC species in trachea and lung. In isolated lungs, the amount of alveolar surfactant harvested by BAL corresponded to 1.62 ± 0.28 µmol of PL, which largely exceeded the amount of PL in the whole rat trachea (see above). Because of the small amounts of PL in tracheal secretions of rats and superfusion of the trachea with culture medium from the luminal side for the optimization of organ culture conditions, we could not measure the amount and composition of tracheal secretions. Instead, we analyzed the secretion of [methyl-3H]choline-labeled, i.e., newly synthesized, PC after addition of unlabeled PL as a carrier to the samples containing airway secretions. After 3 h of organ culture, the [methyl- 3H]choline label of PC in tracheal secretions was only 0.45 ± 0.24% of the total label of tracheal tissue. By contrast, BALF from isolated lungs contained 2.27 ± 0.24% (n = 8) of total pulmonary PC label (P < 0.0001).
Detailed analysis of [methyl-3H]choline incorporation into individual PC species of tracheal and alveolar secretions (Fig. 6B) revealed a completely different pattern of labeling. The fractional label of PC16:0/16:0, PC16:0/14:0, and PC16:0/16:1 in BALF was superior to that in lung tissue and comprised 44.1 ± 3.4, 9.7 ± 0.9, and 20.2 ± 2.6%, respectively, in relation to total PC (each P < 0.001). For all other PC species, the fractional label was lower in BALF than in lung tissue. In contrast, the fractional labels of PC16:0/16:0, PC16:0/14:0, and PC16:0/16:1 in tracheal secretions were not increased over those in tracheal tissue (12.4 ± 1.5, 4.5 ± 0.1, and 7.3 ± 0.8%, respectively, P > 0.05) and were much lower than in BALF (P < 0.001). Instead, PC [methyl-3H]choline label of tracheal secretions reflected the high incorporation of label into the unsaturated PC species of the underlying tissue. Only the essential membrane component PC16:0/20:4 was decreased compared with the amount in the trachea (5.5 ± 2.8 vs. 13.8 ± 0.8%, P < 0.01). Again, in tracheal secretions, incorporation of the [methyl-3H]choline label was significantly higher for PC18:0/18:1, PC18:0/18:2, and other PC species that comprised only a minor fraction of alveolar surfactant.
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DISCUSSION |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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Because of selective storage and secretion, fractional concentrations of secreted PL are different from those of the underlying tissue. This was shown for pulmonary surfactant, inasmuch as PC16:0/16:0, PC16:0/14:0, PC16:0/16:1, and phosphatidylglycerols are preferentially stored in the lamellar bodies of type II alveolar cells and secreted into the alveolar space (1, 6). Nevertheless, lung tissue is enriched in those components, which it preferentially secretes. The principle that PL molecular species of secretions are enriched in the underlying tissue also applies for other organs. The PC species preferentially secreted into the gastric lumen, namely, PC16:0/18:1 and PC16:0/18:2, are also major tissue components, whereas the selective nature of such secretion results in a retention of the highly unsaturated PC species PC16:0/20:4 and PC18:0/20:4. In contrast to the lung, neither mucosa nor secretions from the stomach or eustachian tube contain significant amounts of PC16:0/16:0 (10, 36). Similar data have also been demonstrated for liver compared with bile PL (16, 29).
In airways, the situation is different, inasmuch as in healthy porcine lungs there is no relation between the PL composition of the surfactant fraction on their surface and that of the underlying tissue. Although the PL of airway aspirations are very similar to those of alveolar surfactant, the underlying airway mucosa contains negligible amounts of those PL characteristic of alveolar surfactant or lung parenchyma, particularly PC16:0/16:0. Instead, similar to gastric mucosa, porcine airway mucosa is enriched in mono- and polyunsaturated PC species (7, 10). Moreover, there is no principal difference in mucosal PL between larger and smaller airways: both contain small amounts of PC16:/16:0 and high proportions of unsaturated PC species (7). The data on the composition and metabolism of individual PC molecular species in rat trachea compared with lung parenchyma support our previous measurements in porcine lungs. Again, in tracheal mucosa, the composition of PC molecular species was very different from that of lung parenchyma (see RESULTS) and lung lavage surfactant (8), comprising high concentrations of mono- and polyunsaturated PC species, with low concentrations of PC16:0/16:0. As in the pig, PC composition of rat trachea was similar to that of rat gastric mucosa, where PC16:0/16:0 is a negligible component (10, 19). Because the distribution of cells significantly differs between the trachea and peripheral conducting airways, different characteristics of PL metabolism in these locations cannot be discounted. However, no surfactant-producing cell comparable to the type II alveolar cell has been reported in airways (18, 32). Although Clara cells apparently release surfactant proteins, they do not secrete PL (45). Similarly, the eustachian tube, where cuboidal cells contain granular organelles, was believed to produce surfactant-like material. However, eustachian tube surfactant is mainly composed of unsaturated PC species, instead of PC16:0/16:0.
We used a labeling time of 3 h to investigate the PL metabolism of isolated
tracheae compared with lungs. This ensured morphological and metabolic
integrity of the organs, and from other studies using isolated organs or
cells, linear incorporation of [methyl-3H]choline over
6-24 h can be assumed (12,
39). Because of the rapid
turnover of plasma choline in vivo
(15), however, incorporation
of [methyl-3H]choline into lung tissue PC reaches a
plateau after 3 h; this plateau is maintained for 24 h in in vivo
experiments using mice (37).
Initial [methyl-3H]choline incorporation into individual
PC species, compared with their molar fraction in relation to total PC, was
higher for unsaturated PC species, which are synthesized de novo. By contrast,
for PC16:0/16:0, which in part is synthesized from unsaturated PC via acyl
remodeling, fractional labeling was initially low (24%), and equilibrium with
the molar fraction of PC16:0/16:0 (38%) was completed only after 24 h
(5,
6). Similarly, in perfused rat
lungs, the fractional label of PC16:0/16:0 (28%;
Fig. 6) was lower than its
molar fraction (36%; Fig. 2).
However, in isolated trachea, [methyl-3H]choline
incorporation comprised only 10.6 ± 0.3% for PC16:0/16:0, and
fractional incorporations into PC species were almost identical to their
respective molar fractions after 3 h of radiolabeling. These data indicate
equilibrium between pool fractions and fractional synthesis and exclude
accumulation of isolated components by acyl remodeling at a later time. By
contrast, the fraction of [methyl-3H]choline-labeled
PC16:0/16:0 of trachea decreased at 1.5-3 h of culture, indicating removal of
primarily formed PC16:0/16:0. This is similar to the stomach, where
PC16:0/16:0 does not accumulate, newly synthesized PC16:0/16:0 is rapidly
degraded, and virtually no PC16:0/16:0 is secreted
(10,
43).
Compared with lung tissue, PC from BALF was enriched in [methyl-3H]choline-labeled PC16:0/16:0, PC16:0/14:0, and PC16:0/16:1 at the expense of other PC molecular species such as PC16:0/18:1. In tracheal secretions, however, the label of PC16:0/16:0, PC16:0/14:0, and PC16:0/16:1 was as low as in tracheal tissue. Instead, PC16:0/18:1 was a major component of tracheal secretions, such as in the stomach and eustachian tube (10, 36). Consequently, we postulate that tracheal mucosa does not accumulate PC16:0/16:0 and does not significantly contribute to airway surfactant. In support of this view, airway epithelium and glandular tissue lack lamellar bodies characteristic of surfactant secretion. Moreover, significant contributions of a specialized airway cell type to PC16:0/16:0 of airway surfactant would imply increased synthesis and storage of PC16:0/16:0, which should be detectable by labeling in vivo with radioactive precursors followed by autoradiography (18, 32). Nevertheless, our observations support the hypothesis that some sorting and selective release of individual PC species may occur in the trachea, inasmuch as the label of the cell membrane component PC16:0/20:4 is decreased in tracheal secretions over tissue. The [methyl-3H]choline-labeled PC fraction in tracheal secretions, compared with labeled PC in the whole trachea, was significantly lower than the labeled PC fraction in BALF than in the whole lung. However, the kinetics of PL secretion in the trachea may differ from the kinetics of PL secretion in lung parenchyma. Therefore, we cannot preclude the possibility that, at later time points, the fraction of labeled PC in tracheal secretions would have increased. This may explain the small differences in the PC composition of crude tracheal aspirations compared with surfactant preparations isolated from such aspirations.
In summary, we conclude that there is an essential difference in PC composition and metabolism between rat trachea and lung parenchyma, but there is a similarity between the stomach and the eustachian tube. Although we cannot finally exclude that PL metabolism in more peripheral parts is different from that in the trachea, our experiments show that airway mucosa predominantly synthesizes and secretes unsaturated PC species, rather than PC16:0/16:0, and that conductive airway surfactant probably originates from the alveolar spaces.
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DISCLOSURES |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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ACKNOWLEDGMENTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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REFERENCES |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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-Adrenergic priming of rats in
vivo modulates the effect of -agonists in vitro on surfactant
phospholipid metabolism of isolated lungs. Eur J Clin
Invest 24:
393-399, 1994.[ISI][Medline]
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