Surface Activity Of Pulmonary Surfactant Research Articles

The effect of temperature and breathing pattern on the surface activity of ground squirrel pulmonary surfactant.

This study investigates how hibernation affects the surface activity of pulmonary surfactant with respect to temperature and breathing pattern. Surfactant was isolated from a hibernating species, the 13-lined ground squirrel, and a homeotherm, the rabbit, and analysed for biophysical properties on a constrained sessile drop surfactometer. The results showed that surfactant from ground squirrels reduced surface tension better at low temperatures, including when mimicking episodic breathing, as compared with rabbit surfactant. In addition, low temperature adaptation was also observed using only the hydrophobic components of surfactant from ground squirrels. Overall, the data support the conclusion that ground squirrel surfactant has adapted to maintain surface activity during low temperature episodic breathing patterns, and that temperature adaptation is maintained with the hydrophobic components of the surfactant.

Meconium Impairs Pulmonary Surfactant by a Combined Action of Cholesterol and Bile Acids

Mechanisms for meconium-induced inactivation of pulmonary surfactant as part of the meconium aspiration syndrome in newborn infants, to our knowledge, are not clearly understood. Here we have studied the biophysical mechanisms of how meconium affects surface activity of pulmonary surfactant and whether the membrane-perturbing effects of meconium can be mimicked by exposure of surfactant to a mixture of bile acids and cholesterol. Surface activity of pulmonary surfactant complexes purified from animal lungs was analyzed in the absence and in the presence of meconium in standard surface balances and in a captive bubble surfactometer. We have also evaluated accumulation of surfactant at the air-liquid interface by what we believe to be a novel microtiter plate fluorescent assay, and the effect of meconium components on surfactant membrane fluidity using Laurdan fluorescence thermotropic profiles and differential scanning calorimetry thermograms. Rapid interfacial adsorption, low surface tension upon film compression, efficient film replenishment upon expansion, and thermotropic properties of surfactant complexes are all adversely affected by meconium, and, in a similar manner, they are affected by cholesterol/taurocholate mixtures but not by taurocholate alone. We conclude that inhibition of surfactant by meconium can be mimicked by a bile salt-promoted incorporation of excess cholesterol into surfactant complexes. These results highlight the potential pathogenic role of cholesterol-mobilizing agents as a crucial factor resulting in cholesterol induced alterations of structure and dynamics of surfactant membranes and films.

Prophylactic Intratracheal Polymyxin B/Surfactant Prevents Bacterial Growth in Neonatal Escherichia coli Pneumonia of Rabbits

In neonatal pneumonia, the surface activity of pulmonary surfactant is impaired and microorganisms may invade by passing the air-liquid interface. Previously, we have shown that addition of the antimicrobial peptide polymyxin B (PxB) to modified porcine surfactant (pSF) improves resistance to surfactant inactivation in vitro while antimicrobial activity of PxB is maintained. In this study, we investigated pSF/PxB in vivo. Neonatal near-term rabbits were treated with intratracheal pSF and/or PxB. Rabbits treated with only saline served as controls. Animals were ventilated with standardized tidal volumes and received ∼10(7) Escherichia coli intratracheally. Plethysmographic pressure-volume curves were recorded every 30 min. After 240 min, animals were killed, the right lung and left kidney were excised, and bacterial growth was determined. The left lung was used for histologic analysis. Intratracheal administration of PxB ± pSF significantly reduced the growth of E. coli compared with control animals or animals receiving only pSF. This was accompanied by reduction of severe inflammatory tissue destruction and significantly reduced bacterial translocation to the left kidney. Animals receiving pSF + PxB had no difference in lung compliance compared with the pSF- or PxB-treated group. Mixtures of PxB and pulmonary surfactant show antimicrobial effects in neonatal rabbits and prevent systemic spreading of E. coli.

Functional importance of the NH2-terminal insertion sequence of lung surfactant protein B

Lung surfactant protein B (SP-B) is required for proper surface activity of pulmonary surfactant. In model lung surfactant lipid systems composed of saturated and unsaturated lipids, the unsaturated lipids are removed from the film at high compression. It is thought that SP-B helps anchor these lipids closely to the monolayer in three-dimensional cylindrical structures termed "nanosilos" seen by atomic force microscopy imaging of deposited monolayers at high surface pressures. Here we explore the role of the SP-B NH(2) terminus in the formation and stability of these cylindrical structures, specifically the distribution of lipid stack height, width, and density with four SP-B truncation peptides: SP-B 1-25, SP-B 9-25, SP-B 11-25, and SP-B 1-25Nflex (prolines 2 and 4 substituted with alanine). The first nine amino acids, termed the insertion sequence and the interface seeking tryptophan residue 9, are shown to stabilize the formation of nanosilos while an increase in the insertion sequence flexibility (SP-B 1-25Nflex) may improve peptide functionality. This provides a functional understanding of the insertion sequence beyond anchoring the protein to the two-dimensional membrane lining the lung, as it also stabilizes formation of nanosilos, creating reversible repositories for fluid lipids at high compression. In lavaged, surfactant-deficient rats, instillation of a mixture of SP-B 1-25 (as a monomer or dimer) and synthetic lung lavage lipids quickly improved oxygenation and dynamic compliance, whereas SP-B 11-25 surfactants showed oxygenation and dynamic compliance values similar to that of lipids alone, demonstrating a positive correlation between formation of stable, but reversible, nanosilos and in vivo efficacy.

Inactivation of pulmonary surfactant by silicone oil in vitro and in ventilated immature rabbits

Surface activity of pulmonary surfactant is impaired by exposure to syringes lubricated with silicone oil (SO). These syringes are used daily in clinical practice. In vitro experiments were used for detection of SO, determination of surface activity, and semiquantitative measurement of surfactant protein (SP)-B and -C in SO/surfactant mixtures. Randomized, controlled animal studies were applied for determination of in vivo activity. University research laboratory. Mass spectrometry of SO originating from syringes with and without surfactant was performed. The surface activity of SO plus surfactant phospholipids (PLs) or modified natural surfactant (Curosurf) was measured. SO/Curosurf preparations were further analyzed for changes in the content of SP-B and SP-C using immunoblotting. Neonatal rabbits received mixtures of SO/Curosurf (ratio 0-1.3 mg/mg PL) intratracheally and were then ventilated with a standardized sequence of peak insufflation pressures. Tidal volume curves were recorded, gas volumes of excised lungs were measured, and histologic analysis was performed. Dissolved SO was found after rinsing syringes with organic solvents or Curosurf. Surface activity of Curosurf was significantly reduced after addition of 0.13-1.3 mg SO/mg PL. Immunoblotting revealed interference of SO with SP-B, but not with SP-C. With increasing SO/Curosurf ratios, patchy alveolar air expansion was observed, lung gas volumes were reduced, and time to inflate the lungs was increased, whereas compliance and tidal volumes remained unimpaired. In vitro SO impairs surface activity of Curosurf and leads to interference with SP-B. SO contamination of exogenous surfactant impairs lung function in animal studies and should be avoided.

Critical Structure-Function Determinants within the N-Terminal Region of Pulmonary Surfactant Protein SP-B

Surfactant protein SP-B is absolutely required for the surface activity of pulmonary surfactant and postnatal lung function. The results of a previous study indicated that the N-terminal segment of SP-B, comprising residues 1–9, is specifically required for surface activity, and suggested that prolines 2, 4, and 6 as well as tryptophan 9, may constitute essential structural motifs for protein function. In this work, we assessed the role of these two motifs in promoting the formation and maintenance of surface-active films. Three synthetic peptides were synthesized including a peptide corresponding to the N-terminal 37 amino acids of native SP-B and two variants in which prolines 2, 4, 6, or tryptophan 9 were substituted by alanines. All three synthetic peptides were surface-active, as expected from their amphipathic structure. The peptides were also able to insert into dipalmitoylphosphatidylcholine/palmitoyloleoylphosphatidylglycerol (7:3 w/w ratio) monolayers preformed at pressures >30 mN/m, indicating that they perturb and insert into membranes. Substitution of alanine for tryptophan at position 9 significantly decreased both the rate of adsorption/insertion of the peptide into the interface and reinsertion of surface-active material excluded from the film during successive compression-expansion cycles. Substitution of alanines for prolines at positions 2, 4, and 6 did not produce substantial changes in the rate of adsorption/insertion; however, reinsertion of surface-active material into the expanding interface film was not as effective as in the presence of the nativelike peptide. These results suggest that W9 is critical for optimal interface affinity, whereas prolines may promote a conformation that facilitates rapid insertion of the peptide into phospholipid monolayers compressed to the highest pressures during compression-expansion cycling.

The composition of pulmonary surfactant from diving mammals

Maintaining a functional pulmonary surfactant system at depth is critical for diving mammals to ensure that inspiration is possible upon re-emergence. The lipid and protein composition of lavage extracts from three pinniped species (California sea lion, Northern elephant seal and Ringed seal) were compared to several terrestrial species. Lavage samples were purified using a NaBr discontinuous gradient. Concentrations of phospholipid classes and molecular species were measured using electrospray ionisation mass spectrometry, cholesterol was measured using high-performance liquid chromatography, surfactant protein A (SP-A) and SP-B were measured using enzyme-linked immunosorbent assays. There were small differences in phospholipid classes, with a lower level of anionic surfactant phospholipids, PG and PI, between diving and terrestrial mammals. There were no differences in PL saturation or SP-A levels between species. PC16:0/14:0, PC16:0/16:1, PC16:0/16:0, long chain PI species and the total concentrations of alkyl-acyl species of PC and PG as a ratio of diacyl species were increased in diving mammals, whereas concentrations of PC16:0/18:1, PG16:0/16:0 and PG16:0/18:1 were decreased. Cholesterol levels were very variable between species and SP-B was very low in diving mammals. These differences may explain the very poor surface activity of pinniped surfactant that we have previously described [Miller, N.J., Daniels, C.B., Schürch, S., Schoel, W.M., Orgeig, S., 2005. The surface activity of pulmonary surfactant from diving mammals. Respir. Physiol. Neurobiol. 150 (2006) 220-232], supporting the hypothesis that pinniped surfactant has primarily an anti-adhesive function to meet the challenges of regularly collapsing lungs.

The surface activity of pulmonary surfactant from diving mammals

Pinnipeds (seals and sea lions) have developed a specialised respiratory system to cope with living in a marine environment. They have a highly reinforced lung that can completely collapse and reinflate during diving without any apparent side effects. These animals may also have a specialised surfactant system to augment the morphological adaptations. The surface activity of surfactant from four species of pinniped (California sea lion, Northern elephant seal, Northern fur seal and Ringed seal) was measured using a captive bubble surfactometer (CBS), and compared to two terrestrial species (sheep and cow). The surfactant of Northern elephant seal, Northern fur seal and Ringed seal was unable to reduce surface tension (gamma) to normal levels after 5 min adsorption (61.2, 36.7, and 46.2 +/- 1.7 mN/m, respectively), but California sea lion was able to reach the levels of the cow and sheep (23.4 mN/m for California sea lion, 21.6 +/- 0.3 and 23.0 +/- 1.5 mN/m for cow and sheep, respectively). All pinnipeds were also unable to obtain the very low gamma(min) achieved by cow (1.4 +/- 0.1 mN/m) and sheep (1.5 +/- 0.4 mN/m). These results suggest that reducing surface tension to very low values is not the primary function of surfactant in pinnipeds as it is in terrestrial mammals, but that an anti-adhesive surfactant is more important to enable the lungs to reopen following collapse during deep diving.

Effects of maternal nicotine exposure on lung surfactant system in rats

Maternal smoking during pregnancy may impair pulmonary function in infants and children, but the exact mechanisms underlying these changes remain to be determined. Timed pregnant Sprague-Dawley rats were injected subcutaneously with nicotine at a dose of 2 mg/kg/day from days 3-21 of gestation. A control group was injected with saline. Nicotine-treated dams had lower body weights than control dams from gestational days 5-21, and the values reached statistical significance on gestational days 17, 20, and 21. Total lung saturated phosphatidylcholine contents tended to be lower in nicotine-exposed rats than in control rats from postnatal day 21, and the values reached statistical significance on postnatal days 35 and 42. Maternal nicotine exposure significantly increased surfactant protein (SP)-A, SP-B, SP-C, and SP-D mRNA expression on postnatal day 7, and decreased SP-A, SP-B, SP-C, and SP-D mRNA expression on postnatal day 14. In conclusion, maternal nicotine exposure during pregnancy reduces lung surfactant lipids and produces variable changes in surfactant protein gene expression during the late postnatal period. As good surface activity of pulmonary surfactant is essential for normal lung function, these results suggest that derangement of the pulmonary surfactant system may be important in the pathogenesis of impaired pulmonary function in children exposed in utero to nicotine.

Alterations in surface activity of pulmonary surfactant in Gould’s wattled bat during rapid arousal from torpor

The small microchiropteran bat, Chalinolobus gouldii, undergoes large daily fluctuations in metabolic rate, body temperature, and breathing pattern. These alterations are accompanied by changes in surfactant composition, predominantly an increase in cholesterol relative to phospholipid during torpor. Furthermore, the surface activity changes, such that the surfactant functions most effectively at that temperature which matches the animal’s activity state. Here, we examine the surface activity of surfactant from bats during arousal from torpor. Bats were housed at 24 °C on an 8:16 h light:dark cycle and their surfactant was collected during arousal (28< T b <32 °C). Surface activity was examined with a Captive Bubble Surfactometer at 24 and 37 °C. Surfactant from arousing bats was more active at 37 °C than at 24 °C, indicated by a lower ST min and reduced film area compression required to reach ST min. It appears that the arousal-induced changes in surfactant composition, i.e., lower levels of cholesterol, inhibit adsorption of surfactant at 24 °C. Furthermore, the alterations in surfactant composition during arousal are very rapid, such that the mixture behaves more like surfactant from warm-active bats, and therefore, functions more effectively at 37 °C.

This Month in the Journal

This Month in the Journal

Short-Term Ozone Exposure Affects the Surface Activity of Pulmonary Surfactant

The effects of short-term ozone exposure on the lung function and surface activity of surfactant subtypes isolated from rat lung lavage were studied. Rats were exposed to 0.8 ppm ozone for 2 or 12 hr. The surface activity of surfactant was affected by ozone exposure, whereas distinct morphological changes in bronchoalveolar lavage or in the surfactant subtypes were not observed. Adsorption experiments indicated that bronchoalveolar lavage from rats exposed for 12 hr to ozone remained at lower equilibrium surface pressures than lavage from control rats. These observations suggest interference of inflammatory proteins with the surface film. Extracted surfactant, containing only lipids and surfactant proteins B and C, had a decreased adsorption rate after ozone exposure. These results suggest that the activity of one or both of the hydrophobic surfactant proteins (SP-B and SP-C) was affected by ozone.

Inhibition of pulmonary surfactant biophysical activity by cationic polyamino acids.

The purpose of this study is to investigate the interaction of cationic polyamino acids, polylysine and polyarginine, with rat pulmonary surfactant at the air/water interface. Surface pressure measurements of rat pulmonary surfactant in the presence and absence of polyamino acids were carried out in both dynamic and static modes. In dynamic cycle studies, compression and expansion of adsorbed surfactant films in the presence of the cationic polyamino acids resulted in a delayed attainment of the plateau surface pressure. In area studies of spread surfactant films at constant surface pressure, cationic polyamino acids in the subphase resulted in an increase in film area. Increased film area was also observed when a polyamino acid was injected beneath films of dipalmitoyl-phosphatidylcholine/phosphatidylglycerol. In the presence of the cationic polyamino acids, the equilibrium surface pressure (at constant film area) of pulmonary surfactant was elevated in a concentration- and molecular weight-dependent manner. These data indicate that the model cationic peptides interact with surfactant lipid, possibly electrostatically with phosphatidylglycerol. It is concluded that the surface activity of pulmonary surfactant is significantly inhibited by the presence of the polycations, possibly by the formation of a mixed lipid/polyamino acid film.

Effects of wood and cotton smoke on the surface properties of pulmonary surfactant

The effects of wood and cotton smoke and several known smoke components on the dynamic surface activity of pulmonary surfactant were characterized with a modified Wilhelmy balance. Surfactant was harvested by saline lavage from dog lungs, placed in the balance and a control surface tension/area isotherm (y-A) and surface tension at minimum area (control y min = 6.6±1.6 dynes/cm) measured. Hysteresis area (HA), recruitment index (RI), and stability index (SI) were calculated. Following control measurements, smoke (wood or cotton) was gently blown over the surfactant in the balance. Similarly, each of the individual smoke components or Liquid smoke (prepared by bubbling wood smoke through saline) were injected onto the balance. Wood smoke significantly ( P < 0.05) altered all surface properties measured, increasing y min (22.0±1.6 dynes/cm) and decreasing HA, RI, and SI as compared to control; cotton smoke exposure had almost no effect on surfactant function. A supplementary dose of surfactant was added to the balance, following wood smoke exposure, which decreased y min (9.4±2.6 dynes/cm, P = NS vs control) but not the other parameters to control. Acrolein, formaldehyde, and HCl had little effect on any of the surface properties measured whereas isobutyraldehyde and liquid smoke altered the y-A curve but did not increase y min. These data demonstrate that wood but not cotton smoke inhibit surfactant function, however, surfactant function can be restored, following deactivation by smoke, suggesting that surfactant replacement therapy for victims of severe smoke inhalation may be of benefit.

In Vitro Inactivation of Pulmonary Surfactant Replacement Preparations by Serum Albumin

Inactivation of the surface activity of pulmonary surfactant by serum proteins is an important part of neonatal respiratory distress syndrome. The ability of serum proteins to diminish the surface activity of surfactant preparations used to treat respiratory distress syndrome has not been fully described. The sensitivity of clinically useful pulmonary replacement preparations beractant (Survanta) and colfosceril palmitate, cetyl alcohol, and tyloxapol (Exosurf) to albumin inactivation was examined in vitro by the Wilhelmy plate technique. At a final lipid concentration of 0.1 mg/mL and in the absence of albumin, both Survanta and Exosurf exhibited equilibrium surface tensions in the range of 35 dynes/cm. In the presence of albumin, range of 35 dynes/cm. In the presence of albumin, the surface tension of Survanta was markedly higher. Maximal response of Survanta to albumin was observed at about 1 mg/mL protein concentration. When the lipid concentration was raised to 0.3 mg/mL, the presence of albumin had little effect. With Exosurf, the presence of albumin resulted in only minor elevations of surface tension, even at an albumin concentration 10-fold greater than that used in the experiments with Survanta. These results indicate that at lipid concentrations of 0.1 mg/mL and less, the surface activity of the bovine purified lung surfactant Survanta is more sensitive to the presence of albumin than is the synthetic preparation Exosurf.

Inhibition of pulmonary surfactant by oleic acid: mechanisms and characteristics.

The inhibitory effects of oleic acid (OA) on the surface activity of pulmonary surfactant were characterized by use of the oscillating bubble surfactometer, the Wilhelmy balance, and excised rat lungs. Oscillating bubble studies showed that OA prevented lavaged calf surfactant [0.5 mM phospholipid (PL)] from lowering surface tension below 15 mN/m at or above a molar ratio of OA/PL = 0.5. In contrast to inhibition of surfactant by plasma proteins, increasing the surfactant concentration did not eliminate inhibition by oleic acid, which occurred at OA/PL greater than 0.67 on the oscillating bubble even at surfactant concentrations of 1.5 and 12 mM PL. Studies of surfactant adsorption showed that preformed films of OA had little effect on the adsorption of pulmonary surfactant. Wilhelmy balance studies showed that OA did interfere with the ability of spread films of surfactant to reach low surface tensions during dynamic compression. Further balance experiments with binary films of OA and dipalmitoyl phosphatidylcholine showed that these compounds were miscible in surface films. Together these findings suggested that OA inhibited pulmonary surfactant activity by disrupting the rigid interfacial film responsible for the generation of very low surface tension during dynamic compression. Mechanical studies in excised rat lungs showed that instillation of OA gave altered deflation pressure-volume characteristics with decreased quasi-static compliance, indicating disruption of pulmonary surfactant function in situ. This alteration of mechanics occurred without major changes in the composition of lavaged PLs or in the tissue compliance of the lungs defined by mechanical measurements during inflation-deflation with saline.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of palmitic acid in pulmonary surfactant: enhancement of surface activity and prevention of inhibition by blood proteins

The surface activity of two surfactant preparations, Lipid Extract Surfactant (LES) and Survanta, was examined during adsorption and dynamic compression using a pulsating bubble surfactometer. At low surfactant phospholipid concentrations (1–2.5 mg/ml), Survanta reduces surface tension at minimum bubble radius faster than LES: however, with continued pulsation LES obtains a lower surface tension. Addition of surfactant-associated protein A (SP-A) to LES significantly reduces the time required to reduce surface tension. Survanta is completely unresponsive to the addition of SP-A in that no further reduction of surface tension is observed. Addition of various blood components has been previously shown to inactivate surfactants in vitro. Addition of fibrinogen to Survanta causes an increase in surface tension when measured in the absence of calcium. When assayed in the presence of calcium, inhibition by fibrinogen is not observed possibly due to aggregation of this protein. Albumin and α-globulin strongly inhibit Survanta at physiological serum concentrations both in the presence and absence of calcium. The surface activity of Survanta is also inhibited by lysophosphatidylcholine (lyso-PC). The role of palmitic acid in the surface activity of pulmonary surfactant was examined by adding palmitic acid to LES. At low phospholipid concentrations addition of palmitic acid (10% w/w of the surfactant phospholipid) greatly enhances the surface activity of LES. Maximal enhancement of surface activity and adsorption was observed at or above 7.5% added palmitic acid (w/w of surfactant lipid). LES supplemented with palmitic acid is more resistant to inhibition by fibrinogen, albumin, α-globulin and lyso-PC than LES alone, however, the counteraction of blood protein inhibition is not as pronounced as that observed with SP-A.

A biophysical mechanism by which plasma proteins inhibit lung surfactant activity

These in vitro experiments study a potential mechanism by which plasma proteins, found in the alveoli during pulmonary edema and hemorrhage, may act to inhibit the surface activity of pulmonary surfactant. The results indicate that the inhibition of the adsorption facility and surface tension lowering ability of a calf lung surfactant extract (CLSE) by albumin, hemoglobin, or fibrinogen may be completely abolished by centrifugation of the protein-surfactant mixture at 12,500 × g. Furthermore, albumin, hemoglobin and fibrinogen (1.25 mg/ml) were shown to inhibit the adsorption of high concentrations of CLSE (0.32 mg/ml), normally unaffected by the addition of exogenous proteins, when the CLSE was injected into the subphase under a preformed protein surface film. Similarly, injection of large amounts of these proteins (2.5 mg/ml) into the subphase beneath a preformed CLSE surface film was without effect, even though the CLSE concentration was only 0.06 mg/ml, a surfactant concentration which is normally inhibited by even small amounts of exogenous protein. Taken together, the data suggest that some proteins may inhibit surfactant function by preventing the surfactant phospholipids from adsorbing to the air-liquid interface, possibly by a competition between the proteins and CLSE phospholipids for space at the air-liquid interface rather than direct molecular interactions between proteins and surfactant.

Divalent cation and hydrogen ion effects on the structure and surface activity of pulmonary surfactant

The structure and surface activity of the extracellular fraction of pulmonary surfactant known as tubular myelin are Ca2+ dependent. Previous studies have demonstrated surfactant-specific proteins with monomeric molecular weights of 28,000-36,000 (SP28-36) are associated with this fraction. In reassembled lipoprotein mixtures, SP28-36 promotes the Ca2+-induced aggregation and surface activity of surfactant lipids, but the detailed interactions between Ca2+, SP28-36, and surfactant lipids have not been established. In this study, we investigated the effect of various cations on the aggregation of surfactant lipid liposomes in the presence of SP28-36. SP28-36 reduced the threshold ion concentration for liposome aggregation from greater than 10 to 0.5 mM for Ca2+, Ba2+, and Sr2+ but not Mg2+ or Mn2+. The liposome aggregation was reversed by ethylenediaminetetraacetic acid and not associated with leakage of carboxyfluorescein. SP28-36 promoted similar liposome aggregation at pH less than 5 in the absence of divalent cations. Surfactant lipids adsorbed slowly to an air-fluid interface in all ionic conditions unless SP28-36 was present. Both Ca2+ and H+ induced rapid lipid adsorption in the presence of SP28-36. The surface activity of native surfactant had a similar ion dependence. Electron micrographs of native surfactant showed typical tubular myelin structures at pH 7.4 only in the presence of Ca2+. At pH 4.4 in the absence of Ca2+, similar but not identical structures were seen. In the reconstituted system, SP28-36 in the presence of Ca2+ induced the formation of larger multilayered structures including parallel bilayers and small areas of squares and triangles with dimensions similar to structures found in the native material.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cholesterol and cholesteryl ester on dynamic surface tension of dipalmitoyl lecithin

The lipid composition of cell membranes, serum lipoproteins, and various subcellular particles determines the lipid-lipid interactions that are in part responsiblefor the architecture, and the physical properties (such as plasticity, viscosity, thermal transitions) of the resulting structures as well as for the biochemical function of the related aqueous surfaces. Cholesterol exists free in cell membranes (1), is carried also free and in the form of cholesteryl esters by serum lipoproteins (2), and is found in both forms in pulmonary lavage, which is obtained by irrigation of the lung with 0.15 M NaCI (3, 4) and is known to affect the surface activity of pulmonary surfactant (5, 6). Also known are the binding of cholesterol to phosphatidyl cholines (lecithins) (7-9) and the influence of cholesteryl esters on the equilibrium force-area curves of lecithin's monomolecular films (10). In this communication, we wish to describe the influence of cholesterol and cholesteryl palmitate on the dynamic force-area curve of dipalmitoyl lecithin at 25 and 37°C in a modified Langmuir trough. A similar study, using adsorbed DPL-cholesterol mixed films by the bubble method has been published recently (6). In our approach we study both adsorbed and spread films, whereby we are able to consider the effect of the physical state of the lipid and of the mode in which the lipid is applied to the interface (3, 5). MATERIALS AND METHODS