Lung Surfactant Phospholipids Research Articles

Expression of pulmonary surfactant protein D in rat gastric mucosa.

Gastric mucosa is protected from an acidic lumenal environment by an extracellular layer composed in part of phospholipids that are similar in composition to the phospholipids of lung surfactant. The function and metabolic processing of lung surfactant is regulated, in part, by surfactant specific proteins. We speculated that the gastric extracellular acid barrier might be regulated by such proteins. We demonstrate by RNA blot analysis, RT-PCR, and immunostaining and protein blot the synthesis of surfactant protein D (SP-D) in mucus-secreting cells of the gastric mucosa. SP-D protein and mRNA were not detected in the duodenum and the remainder of the gastrointestinal tract. We speculate that SP-D may participate in the regulation of secretion or assembly of the gastric acid barrier. Alternatively, SP-D may participate in gastric mucosal host defense.

Improved method for quantitative analysis of lung surfactant phospholipids in bronchoalveolar lavage fluids by high-performance liquid chromatography

Improved method for quantitative analysis of lung surfactant phospholipids in bronchoalveolar lavage fluids by high-performance liquid chromatography

Changes in Alveolar Lavage Materials and Lung Microsomal Xenobiotic Metabolism Following Exposures to HCl-Washed or Unwashed Crystalline Silica

Intratracheal exposures of rats to crystalline silica washed with HCl to remove iron contaminants have previously been shown to increase lung surfactant phospholipids (PL) and proteins and to alter the pulmonary microsomal cytochrome P450 system. We compared these effects of HCl-washed silica with those produced by exposures to unwashed silica and alumina. Both silica preparations produce increases in lung weights and alveolar lavage PL and proteins, but to different degrees. The increases produced by HCl-washed vs unwashed silica are lung weights, 2.2- vs 1.3-fold; lavage FL, 25.9- vs 3.7-fold; and lavage proteins, 11.1- vs 3.2-fold, respectively. Although the two silica particles increase lung microsomal protein concentrations (expressed per gram lung) by 50-60%, their effects on cytochrome P-450-mediated xenobiotic metabolism are quite different. Exposure to HCl-washed silica leads to a 2.3-fold increase in 7-ethoxyresorufin O-deethylation, a reaction catalyzed by cytochrome P4501A1, and a 0.5- to 0.6-fold reduction in 7-ethoxycoumarin O-deethylation, a reaction which may be catalyzed by cytochrome P-4502B1. Unwashed silica does not alter the metabolism of either xenobiotic when results are expressed per milligram microsomal protein. Administration of alumina produces only minor increases in lung weight and lavage PL and no effect on microsomal xenobiotic metabolism. These results show that the increases in alveolar lavage PL and proteins induced by administration of unwashed silica are exaggerated by 3- to 7-fold if the silica is treated with HCl. Furthermore, exposure to HCl-washed silica results in significant alterations of the lung microsomal cytochrome P450 system, but the unwashed silica has little effect. Although the reason(s) for these different effects is not known, measurements of iron levels and formation of hydroxyl radicals using ESR demonstrate that there is more iron associated with the unwashed than with the HCl-washed silica.

Retinoids control surfactant phospholipid biosynthesis in fetal rat lung.

Vitamin A (retinol) may play an important role in lung maturation: 1) premature delivery is simultaneously a source of vitamin A deficiency and increased risk of neonatal respiratory distress syndrome and subsequent bronchopulmonary dysplasia (BPD), due to deficit in pulmonary surfactant; 2) neonatal supplementation with retinol reduces the risk of BPD; and 3) fetal rat lung stores retinol in late gestation just before the onset of surfactant synthesis. To test the hypothesis of an implication of retinoids in the control of pulmonary surfactant synthesis, experiments were designed in the pregnant rat, aiming either at enhancing fetal lung vitamin A stores, bringing the active metabolite of vitamin A, retinoic acid (RA), or inhibiting the conversion of retinol to RA with aid of citral. Maternal administration of a single dose of 50,000 IU of retinyl palmitate on day 16 (term 22 days) increased 22 and 29%, respectively, the total phospholipid (TPL) and disaturated fraction of phosphatidylcholine (PC) in extracted fetal surfactant on day 19 but did not change surfactant protein (SP) A concentration. Chronic administration of retinyl palmitate to the mother from day 16 through 20 increased disaturated PC content on day 21 but decreased SP-A concentration. Fetal lung surfactant phospholipids were increased by chronic administration of RA and considerably reduced by citral (-31 and -35% for TPL and PC concns, respectively). RA also enhanced labeled choline incorporation into fetal lung PC on day 20. Given once on day 17, it accelerated the appearance of surfactant precursors on day 18.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis and release of amphipathic gamma-glutamyl transferase by the pulmonary alveolar type 2 cell. Its redistribution throughout the gas exchange portion of the lung indicates a new role for surfactant.

gamma-Glutamyl transferase (gamma-GT) catalyzes a transpeptidation reaction which is involved in the metabolism of glutathione. Glutathione is abundant within the epithelial lining fluid of the lung. However, little is known about gamma-GT expression in the epithelial cells of the lung alveolus. Herein we show that the pulmonary alveolar epithelial type 2 cell expresses the gene for gamma-GT. We were unable to detect expression in the pulmonary alveolar epithelial type 1 cell or in the pulmonary alveolar macrophage. gamma-GT expression in the pulmonary alveolar epithelial type 2 cell is via mRNA III, a transcript that was initially cloned from the liver. This cell synthesizes gamma-GT protein and releases enzyme activity into a surfactant-associated pool within the lung alveolus. The specific activity of this surfactant-associated enzyme is almost 10-fold higher than that of whole lung. This activity results from amphipathic gamma-GT since it partitions with lung surfactant phospholipid and with the detergent phase of Triton X-114. Activity can be dissociated from each by papain proteolysis. These results demonstrate that gamma-GT is expressed in the differentiated pulmonary alveolar epithelial type 2 cell and that amphipathic gamma-GT protein is released by this cell along with lung surfactant. These results suggest that surfactant may serve an expanded role in lung cell biology as the vehicle for the redistribution of amphipathic signal anchored proteins throughout the gas exchange surface of the lung.

The Lung Surfactant and Immune System Response to Intratracheal Administration of “Empty” Liposomes

AbstractAfter intratracheal administration of “empty” lecithin-cholesterol liposomes to rats it was found out twofold enhancement of the surfactant content with maximum on the 2nd-3rd day and with normalization to the control level by the 7th day. Phagocytic index of the alveolar macrophages was also increased. It was shown the change of the blast-transformation reaction of bronchoalveolar lavage and blood lymphocytes. Immune complexes content in bronchoalveolar lavage at different period of time after liposomes administration increased 1.5-2-fold. The natural killers (NK) activity of cells obtained from bronhoalveolar lavage and blood was enhanced 10 times and 2 times respectively. It is supposed that enhancement of lung surfactant phospholipid content is caused by substrate stimulation of type II alveolocytes activity. The stimulation of immunocompetent cells might be connected with imitation of bacterial attack by liposomes with proteins adsorbed on their surface.

Toxicological investigations on silicon carbide. 1. Inhalation studies.

The question of lung damage as a result of exposure to silicon carbide (SiC) was investigated by inhalation experiments to obtain information on the qualitative response of lung tissue to the test substance (SiC). For comparison, quartz, kaolinite, and tempered clay dusts were used. The indices for the effects of the dusts studied were organ weights, numbers of bronchoalveolar cells, lung surfactant phospholipid concentrations including subfractions, and lung clearance. Exposure to the test samples was carried out according to the Essen inhalation model in two independent series. The results of the two series were similar: Compared with sham controls, exposure to SiC did not affect the indices studied. Even at a low dose (a quarter of the SiC dose) quartz gave pronounced deviations in all indices. In particular, an increase in granulocytes indicated toxic properties of the dust. The long term elimination of quartz from the lung was worse than that of SiC. The kaolinite and tempered clay dusts were intermediate between SiC and quartz based on several of the indices studied. It is concluded that SiC is deposited practically inert in the lung.

Lung Surfactant Phospholipids Associate with Polymerizing Fibrin: Loss of Surface Activity

Intraalveolar fibrin formation is a hallmark of many acute and chronic lung inflammatory processes. We investigated the influence of fibrin polymerization on biochemical and biophysical properties of a calf lung surfactant extract (CLSE) used for therapy of neonatal distress syndrome. Thrombin-induced coagulation of human fibrinogen (range, 0.04 to 4 mg/ml) in the presence of CLSE (2 mg/ml phospholipids) resulted in progressive loss of surface tension-lowering properties and adsorption facilities of this surfactant preparation; the CLSE-inhibitory capacity of desAABB-fibrin surpassed that of fibrinogen by more than two orders of magnitude. In parallel with the loss of surface activity, association of the predominant surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) (14C-labeled, admixed to 2 mg/ml CLSE) with polymerizing desAABB-fibrin occurred. A volume of 0.3 mg/ml insoluble fibrin effected a approximately 50% loss, and 0.6 mg/ml a > 90% loss, of DPPC from the aqueous phase. Dioleoylphosphatidylcholine, dipalmitoylphosphatidic acid, stearic acid, palmitic acid, and arachidonic acid, admixed to CLSE as labeled compounds, as well as total CLSE phospholipids were retained in polymerizing desAABB-fibrin with dose-effect curves superimposable to that of DPPC; no fibrin association was noted for 14C-glycerol-3-phosphate. Polymerizing desAA-fibrin, generated by incubation of CLSE-fibrinogen mixtures with arvin, captured DPPC and resulted in loss of surface properties at even lower concentrations, compared with desAABB-fibrin. In contrast, CLSE incubation with preformed desAABB- and desAA-fibrin polymers did not cause substantial phospholipid coupling with the clot material or loss of surface properties. Microtiter plate-immobilized fibrinogen and desAABB- and desAA-fibrinomonomers did not bind CLSE phospholipids enriched with 14C-DPPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone--induced changes in surfactant phospholipids of rat lung.

Amiodarone HCl (AD) is a very effective antiarrhythmic drug, but its use is often associated with serious pulmonary complications. It is shown to induce lung phospholipidosis. Nevertheless, the effects of this drug on pulmonary surfactant which is composed of about 75% phospholipids and which prevents alveolar collapse is not known. Therefore, we have examined the effect of AD on the intra- and extracellular surfactant pools and on the levels of phosphatidylcholine (PC), the primary constituent of pulmonary surfactant. Male Wistar rats were fed AD (175 mg/kg) by oral gavage for three weeks. At the end of the experimental period, the rats were killed, the lungs removed and perfused, and surfactant isolated. Some lungs were prepared for ultrastructural examination. Phospholipid was assayed in the intra- and extracellular surfactant. Amiodarone produced a significant increase in both the intra- and extracellular surfactant phospholipid along with an appreciable change in the phospholipid profile. Also, the drug seemed to increase the number of lamellar inclusions in the surfactant producing type II alveolar cells. These data suggest that administration of AD leads to an increase in the lung surfactant phospholipid levels and lamellar bodies in alveolar type II cells.

The effects of dietary fish oil on alveolar type II cell fatty acids and lung surfactant phospholipids.

The purpose of this study was to determine the responsiveness of alveolar type II cells to dietary fish oil and the consequent effects on alveolar and lung surfactant. Rats were fed a corn oil or a fish oil diet for four weeks. Dietary n-3 fatty acids were readily incorporated into the type II cell phospholipids as indicated by higher levels of eicosapentaenoic acid (2.77 +/- 0.10%) and docosahexaenoic acid (1.63 +/- 0.10%) in the group receiving the fish oil diet. The elevated levels of n-3 fatty acids were accompanied by concomitant reduction in arachidonic acid and linoleic acid. Neither eicosapentaenoic acid nor docosahexaenoic acid was incorporated into type II cell triacylglycerols. Feeding a fish oil containing diet increased surfactant phospholipids, particularly 1,2-disaturated acyl phosphatidylcholines in whole lung compared to a corn oil diet. However, the amount of surfactant found in the alveolus was not different between the two diet treatment groups. The results suggest that dietary n-3 fatty acids stimulate synthesis and/or inhibit degradation of lung surfactant without altering surfactant secretion in alveoli.

Purification, characterization and substrate specificity of rabbit lung phospholipid transfer proteins

Three phospholipid transfer proteins, namely proteins I, II and III, were purified from the rabbit lung cytosolic fraction. The molecular masses of phospholipid transfer proteins I, II and III are 32 kilodaltons (kDa), 22 kDa and 32 kDa, respectively; their isoelectric point values are 6.5, 7.0 and 6.8, respectively. Phospholipid transfer proteins I and III transferred phosphatidylcholine (PC) and phosphatidylinositol (PI) from donor unilamellar liposomes to acceptor multilamellar liposomes; protein II transferred PC but not PI. All the three phospholipid transfer proteins transferred phosphatidylethanolamine poorly and showed no tendency to transfer triolein. The transfer of [ 14C]PC from unilamellar liposomes to multilamellar liposomes facilitated by each protein was affected differently by the presence of acidic phospholipids in the PC unilamellar liposomes. In an equal molar ratio of acidic phospholipid and PC, phosphatidylglycerol (PG) reduced the activities of proteins I and III by 70% ( P = 0.0004 and 0.0032, respectively) whereas PI and phosphatidylserine (PS) had an insignificant effect. In contrast, the protein II activity was stimulated 2–3-times more by either PG ( P = 0.0024), PI ( P = 0.0006) or PS ( P = 0.0038). In addition, protein II transferred dioleoylPC (DOPC) about 2-times more effectively than dipalmitoylPC (DPPC) ( P = 0.0002), whereas proteins I and III transferred DPPC 20–40% more effectively than DOPC but this was statistically insignificant. The markedly different substrate specificities of the three lung phospholipid transfer proteins suggest that these proteins may play an important role in sorting intracellular membrane phospholipids, possibly including lung surfactant phospholipids.

An X-ray reflectivity investigation of a deposited layer of the natural lung surfactant

The morphology of natural lung surfactant and of two of its constituents, dioleylphosphatidylcholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC), respectively representative of the unsaturated and saturated phospholipids of natural lung surfactant, has been investigated by X-ray reflectivity. Since the behavior of lung surfactant in in vivo dynamic conditions may be modeled by the compression-decompression of monolayers spread at the air-water interface, Langmuir-Blodgett sampling has been used to characterize its structures. The results reveal that the natural lung surfactant forms a monolayer covered with some crystallites, while DOPC forms a homogeneous monolayer, and DPPC piles up in multilayers. These results are related to the respreading mechanism of the studied monolayers.

Fetal lung development in rats with a glycogen storage disorder

A New Zealand strain of rats (NZR/Mh) is unable to mobilize liver glycogen due to a deficiency of phosphorylase b kinase. Affected homozygous rats (gsd/gsd) were used to assess the developmental relationship between lung glycogen loss and surfactant phospholipid and protein biosynthesis. Phosphorylase a and phosphorylase b kinase activities were negligible in gsd/gsd fetal lungs compared with controls from gestational day (D18) until postnatal day 1 (D + 1). At D20, tissue glycogen content was 158 +/- 5 and 181 +/- 6 mumol/g lung for control and gsd/gsd, respectively. Control rats mobilized 84% of their lung glycogen by D + 1, whereas the gsd/gsd strain retained 70-80% of D19-20 levels. This apparent fall in gsd/gsd glycogen per gram lung was due to an increase in cellular protein and size. Thus, in controls, total glycogen per lung decreased 65% from D20 to D + 1, whereas DNA doubled. In contrast, gsd/gsd lung growth resulted in a doubling of total lung glycogen, whereas the glycogen-to-DNA ratio remained constant. A lack of cellular glycogenolysis was confirmed by electron microscopy where gsd/gsd type II cells remained large and glycogen-rich over the entire perinatal interval. The potential for glycogen breakdown by a lysosomal alpha-amyloglucosidase in gsd/gsd lungs was estimated in tissue homogenates, whereas rates of hydrolysis of glycogen or p-nitrophenylglucoside were significant and equal to controls at all ages tested. Incorporation of [14C]choline into phosphatidylcholine (PC) of incubated lung slices increased 1.7-fold in control lungs from D20-D21. Over the same interval, PC synthesis in gsd/gsd lungs was 40% lower and did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical synthesis and surface activity of lung surfactant phospholipid analogs. II. Racemic N-substituted diether phospholipids

A series of racemic 16:0 disaturated N-substituted diether phosphonolipid analogs of glycerophospholipids have been synthesized and purified. Isosteric methylene substitution at three of the four ester sites (carboxyl, phosphate) of conventional glycerophospholipids enhanced the hydrophobicity of analog compounds compared with dipalmitoyl phosphatidylcholine (DPPC), the major glycerophospholipid component of lung surfactant. Further substitutions at the nitrogen headgroup also contributed to hydrophobicity/hydrophilicity characteristics, as well as allowing graded variations in headgroup size among the members of the diether phosphonolipid analog series. Interfacial property studies showed that these compounds had significant differences in surface activity characteristics compared with DPPC, including increased adsorption and respreading facility, plus an enhanced ability to generate low surface tension (< 1 to 4 mN/m) on an oscillating bubble apparatus at 37°C. In addition, pressure-volume mechanical studies in surfactant-deficient excised rat lungs showed that the diether phosphonate analog of DPPC could partially restore pressure-volume characteristics toward normal, both as a pure component and in binary could partially restore pressure-volume characteristics toward normal, both as a pure component and in binary mixtures with palmitoyl-oleoyl phosphatidylglycerol. These findings suggest that selected analog compounds, synthesized with relatively small structural modifications from biologic glycerophospholipids, may have eventual applications as components of synthetic exogenous lung surfactants. Of more immediate importance, analog molecules with defined structural variations are convenient molecular probes for developing structure-surface activity correlates for phospholipid-like surfactants and for investigating the specificity of interactions between glycerophospholipids and other compounds such as proteins.

Chemical synthesis and surface activity of lung surfactant phospholipid analogs. III. Chiral N-substituted ether-amide phosphonolipids

A homologous series of chiral (R) ether-amide phosphonolipid analogs of naturally occuring (R) glycerophospholipids were synthesized and characterized for their interfacial behaviors. The phosphonolipids possess isoteric ether, amide, and phosphonate functions at positions corresponding to the sn-1, sn-2, and sn-3 ester functions, respectively , of naturally occurring glycerophospholipids. All compounds were synthesized with disaturated C16:0 alkyl/acyl moieties to give structural analogy with dipalmitoyl phosphatidylcholine (DPPC), the major glycerophospholipid component of lung surfactant. Further substitutions at the headgroup nitrogen were also used to generate differences in headgroup size and polarity in the synthetic compounds. The surface activity of the ether-amide phopholipids was investigated in terms of adsorption to the air-water interface, together with studies of dynamic respreading after monolayer collapse and surface tension lowering in dynamically compressed spread films and dispersions. Results showed that several ether-amide phosphonolipids had more rapid adsorption and improved dynamic respreading behavior compared to DPPC, plus the ability to lower surface tension into the range of <1 to 4 mN/m in spread films and in dispersions under dynamic conditions. In combination with a series of diether phosphonolipids synthetized in a companion study [1], these ether-amide compounds are useful in the development of molecular stracture-surface activity correlates for lung surfactant-related materials, and should assist in investigating the specificity of interactions between phospholipids and other pulmonary biological molecules

Radiolabeling of the hydrophobic components of lung surfactant with 3-(trifluoromethyl)-3-( m-[ 125I]iodophenyl)diazirine

Studies of the metabolism and distribution of lung surfactant are aided by use of radiolabeled surfactant or surfactant components. These studies have often made use of [ 3H]- or [ 14C]phosphatidylcholine. Analysis of the lung content of surfactant containing these β-emitting labels usually requires tissue digestion, use of scintillation fluids, and significant correction for quenching of photon production. Because use of a γ-emitting isotope would obviate these requirements, we have investigated the use of 3-(trifluoromethyl)-3-( m-[ 125I]iodophenyl)diazirine ([ 125I]TID), a lipophilic photoactivatable compound, to radiolabel pulmonary surfactant. Our results indicate that, during photoactivation, products of [ 125I]TID are produced that result in radiolabeling of both the lipid and protein components of extracted porcine surfactant. Separation of radiolabeled surfactant from hydrophobic nonlabeling photolysis products was accomplished by gel chromatography. Exposure of surfactant (34 μmol/ml) to [ 125I]TID under labeling conditions resulted in incorporation of 45.3 ± 5.1% of the radiolabel. Incorporation of radiolabel in the various phospholipids of lung surfactant was approximately equivalent. Lipophilic surfactant apoproteins were also radiolabeled. Finally, both in vitro and in vivo testing of radiolabeled surfactant (0.1 μCi/mg) revealed full retention of surface tension lowering ability.

The Usefulness of Lung Surfactant Phospholipids (LSPs) in the Diagnosis of Drowning

The authors have studied the usefulness of some lung surfactant phospholipids (LSPs) isolated from lung tissues as markers of drowning. Two different groups of rabbits were sacrificed by drowning in fresh and salt water, and their phospholipid compositions were compared with those of a non-drowned control series. For the phospholipids studied in lung lavages (phosphatidyl choline, phosphatidyl ethanolamine, and phosphatidyl glycerol) the proportions differed between the control group and the drowned group, and between the fresh-water and salt-water drowned animals. According to these results, the lipids we have analyzed can be employed as markers in forensic autopsies, where it is necessary to differentiate between death by drowning and postmortem immersion and between fresh-water and salt-water drowning. In lung tissue, only phosphatidyl choline and phosphatidyl inositol showed significative differences. These results also confirm that LSPs are strongly affected in drowning.

Hydrophobic homopolymeric peptides enhance the biophysical activity of synthetic lung phospholipids

The effects of homopolymeric amino acids (molecular weight 2300 to 14,000) on the surface activity of dipalmitoyl phosphatidylcholine (DPPC) and DPPC/egg-phosphatidylglycerol (PG) were characterized by adsorption and dynamic surface tension lowering measurements at 37°C. Homopolyamino acids studied included poly l-leucine (poly-Leu) and poly- l-valine (poly-Val), since Leu and Val are known to be prominent in the structure of hydrophobic lung surfactant apoprotein SP-B and SP-C. In addition, several other homopolyamino acids with varying hydrophobicity index were also investigated, including poly- l-phenylalanine (poly-Phe), poly- l-serine (poly-Ser), poly- l-lysine (poly-Lys) and poly- l-glutamic acid (poly-Glu). Results showed that hydrophobic poly-Leu and poly-Phe at 1 and 10 weight percent greatly increased the adsorption facility of DPPC and DPPC/PG mixtures, with maximum surface pressures (up to 49 mN/m) near the equilibrium limit for phospholipid systems. In oscillating bubble studies, 1% mixture of poly-Leu or poly-Phe with DPPC or 8:2 DPPC/PG lowered surface tension into the range (near 1 mN/m) associated with active lung surfactant. In contrast, mixtures of DPPC and DPPC/PG with the more hydrophilic peptides poly-Ser, poly-Lys and poly-Glu showed little or no enhancement of surface activity over the phospholipids alone. Mixtures of poly-Val and phospholipids did not combine well with the simple co-sonication procedure used, and also exhibited little improvement in surface activity. Taken together, these results suggest that dydrophobicity is an important determinant for interactions of proteins with lung surfactant phospholipids, and that significant biophysical activity effects are not limited to highly specific amino acid sequences of the surfactant apoproteins, SP-B and SP-C. Simple homoamino acid polymers may provide useful model systems for investigating the specificity and character of some of these interactions, as well as the effectiveness of protein- phospholipidcombination in synthetic surfactant mixtures.

Initiation of fetal rat lung phospholipid and surfactant-associated protein A mRNA synthesis.

To determine whether the initiation of fetal lung surfactant phospholipid production and the activation of the gene for the 35-kD surfactant-associated protein are dependent on circulating corticosteroids, we cultured dexamethasone-responsive explants of 15- to 17-d fetal rat lung in medium with 1% FCS (controls), charcoal-stripped 1% FCS, or a variety of glucocorticoid antagonists. The steroid antagonist RU 486 almost completely abolished specific cytoplasmic and nuclear dexamethasone binding in the explants but had no glucocorticoid-agonist activity. There was a significant increase in disaturated phosphatidylcholine synthesis during 7 d in culture in control explants (78%) and in those cultured with Charcoal-stripped serum (83%), RU 486 (82%), or the other glucocorticoid antagonists--clotrimazole, cortexelone, and 11-ketoprogesterone. Specific mRNA for surfactant-associated protein A was not detectable in preculture 17-d lung tissue, but accumulated to the same extent in cultures with or without RU 486 in the medium. These findings support the view that expression of the genes responsible for the synthesis of the various components of surfactant is not induced by glucocorticoids, but by signals contained within the lung tissue itself. The role of circulating hormones is later acceleration and modulation of surfactant production.

Pulmonary surfactant. II. In sudden infant death syndrome

The lung surfactant phospholipid composition of lavage samples from 102 babies dying from Sudden Infant Death Syndrome (SIDS) (one-third with minor signs of inflammation) was compared with that of: 34 babies dying from Hyaline Membrane Disease (HMD), 15 mature babies dying soon after birth, 16 mature babies dying in the same age range as the sudden infant death syndrome cases, 13 babies dying from pneumonia and 6 from septicaemia. The surfactant of the two groups of babies dying from SIDS was identical and approximated that obtained from babies dying from HMD, pneumonia or septicaemia. Compared to that obtained from mature babies, the surfactant of babies dying from SIDS contained significantly lower proportions of phosphatidylcholine (PC) and significantly higher proportions of lyso-PC and sphingomyelin. The proportion of disaturated PC was similar to that of the surfactant of the age-matched mature babies. The surfactant composition of the babies dying from SIDS did not change appreciably after death nor vary with age at death. The surfactant phospholipid composition of postmortem samples from mature babies was similar to that of aspirates from living babies and infants and to that of bronchoalveolar lavage samples from living adults.