Turnover of cholesterol and dipalmitoyl phosphatidylcholine in surfactant of adult rat lung

In order to compare the turnover of two major surfactant components, [1α,2α(n)-³H]cholesterol and [methyl ¹⁴ C choline] dipalmitoyl phosphatidylcholine (DPPC) were introduced as lamellar bodiesvia the trachea into lightly anesthetized rats which were then allowed to recover. The radiotracers were assumed to have entered the alveolar surfactant pool and to have subsequently recycled in part into the lamellar bodies of alveolar type II cells. For DPPC, the specific activityvs. time curves of tubular myelin rich (alv-1) and tubular myelin poor (alv-2) alveolar lavage fractions were similar, and there was a plausible precursor-product relationship between lamellar bodies and either (or both) of these compartments. In contrast, however, the specific activities of alv-1 and alv-2 for cholesterol were quite different, allowing us to reject the hypothesis of a precursor-product relationship between classical lamellar bodies and alv-2. The estimated turover time for DPPC in alv-1 was 240 or 206 min, depending on which subfraction of lamellar bodies one takes to be the precursor. For cholesterol it was 583 or 624 min. These longer turnover times for cholesterol should lead to a greater than twofold increase in the relative concentration of cholesterol in the putative product compartment. Such an increase was not found. We interpret this as reflecting either noncompartmental behavior of the alveolar surfactant pool, or multiple pools of lamellar bodies with different turnover times. We conclude that two major components of pulmonary surfactant, cholesterol and DPPC, are handled differently, and that for at least one of these substances, the widely accepted scenario of a compartmental precursor-product relationship between lamellar bodies and alveolar surfactant must be rejected.     

Coordinate packaging of newly synthesized phosphatidylcholine and phosphatidylglycerol in lamellar bodies in alveolar type II cells

Methylamine, a weak base, inhibits packaging of newly synthesized phosphatidylcholine (PC) in lamellar bodies in 20–22 h cultured alveolar type II cells, suggesting a role for acidic pH of lamellar bodies. In this study, we tested if (i) the packaging of PC is similarly regulated in freshly isolated type II cells and (ii) methylamine also inhibits the packaging of other surfactant phospholipids, particularly, phosphatidylglycerol (PG). The latter would suggest coordinated packaging so as to maintain the phospholipid composition of lung surfactant. During the short-term metabolic labeling experiments in freshly isolated type II cells, methylamine treatment decreased the incorporation of radioactive precursors into PC, disaturated PC (DSPC), and PG of lamellar bodies but not of the microsomes, when compared with controls. The calculated packaging (the percentage of microsomal lipid packaged in lamellar bodies) of each phospholipid was similarly decreased (∼50%) in methylamine-treated cells, suggesting coordinated packaging of surfactant phospholipids in lamellar bodies. Equilibrium-labeling studies with freshly isolated type II cells (as is routinely done for studies on surfactant secretion) ± methylamine showed that in methylamine-treated cells, the secretion of PC and PG was decreased (possibly due to decreased packaging), but the phospholipid composition of released surfactant (measured by radioactivity distribution) was unchanged; and the PC content (measured by mass or radioactivity) of lamellar bodies was lower, but the PC composition (as percentage of total phospholipids) was unchanged when compared with control cells. We speculate that the newly synthesized surfactant phospholipids, PC, DSPC, and PG, are coordinately transported into lamellar bodies by a mechanism requiring the acidic pH, presumably, of lamellar bodies.     

Analysis of subcellular phosphatidyl choline in developing rabbit lung

Phosphatidyl choline is a major lung surfactant. Insufficient development of the surfactant in neonates is often associated with the Respiratory Distress Syndrome. The concentration and fatty acid composition of phosphatidyl choline have not been studied in the subcellular organelles of the developing lung. This study has investigated the development of the concentration and fatty acid composition of phosphatidyl choline in subcellular fractions of 28-day and 30-day fetal and maternal New Zealand rabbit lungs. The concentration of total phospholipids in lamellar bodies increased four to five fold from 28-day fetus to 30-day fetus which, in turn, was similar to the maternal level. Total phospholipid content increased only about 50% in mitochondria and microsomes. The percentage of phosphatidyl choline among total phospholipids in lamellar bodies increased successively from 60% at 28 days gestation to 84% at 30 days gestation and leveled at 84% in maternal lamellar bodies. Microsomal PC increased steadily from 52% in the 28-day fetus to 65% in the adult. Analysis of the fatty acid composition of phosphatidyl choline in lamellar bodies confirmed 16∶0 as the major fatty acid, and its content remained constant from 28 days gestation to adult. In contrast, the content of 16∶0 of the microsomal phosphatidyl choline decreased with increasing gestation. Changes of several unsaturated fatty acid components were observed in both lamellar bodies and microsomes in the developing lungs. Maturational development of phosphatidyl choline is reflected in an increase in the concentration of this surfactant, particularly in lamellar bodies, and possibly in remodeling of fatty acid composition in both lamellar bodies and microsomes.     

Androgen regulation of lung lipids in the male rat

The aim of this study was to determine whether or not testosterone regulates the lipid concentration in rat lung tissue. Rats were either sham-operated controls, castrated, or castrated and injected with testosterone. Twenty-one days after castration, we observed in relation to the control: (i) Total lipids, phospholipids, and total cholesterol increased, while triglycerides decreased in whole lung. (ii) Phospholipid concentration increased in microsomes, lamellar bodies, and alveolar macrophages, but it decreased in extracellular surfactant. (iii) On a percentage basis, the concentration of phosphatidylcholine increased in microsomes, lamellar bodies, and alveolar macrophages, and it decreased in extracellular surfactant. (iv) Protein concentration decreased in extracellular surfactant and increased in microsomes, lamellar bodies, and alveolar macrophages. (v) The incorporation of [¹⁴C]glycerol into phospholipids of lung slices increased. (vi) The activity of CTP:phosphocholine cytidylyltransferase bound to the microsomal fraction increased without any change in the activity of the soluble form of the enzyme in the lung. The results obtained when testosterone was administered to castrated rats were similar to those obtained in the control in all cases. These results suggest that the lipid concentration in the lung is regulated at least partly directly or indirectly by androgens.     

Vitamin E-Stoffwechsel der Lunge

Vitamin E Metabolism of the Lung . Experimental and clinical data have provided evidence for the involvement of oxygen free radicals in the development of acute and chronic lung diseases. Alveolar surfactant is the prime target of oxidative air pollutants. Lung surfactant consists to 90% of lipids and contains vitamin E as most important lipophilic antioxidant. Recently, we showed that alveolar surfactant is supplemented with vitamin E during its synthesis in type II pneumocytes. Hyperoxia is very often a necessary therapeutic intervention which seems to impose oxidative stress on lung tissue. Hyperoxia caused an increase in vitamin E turnover, measured in type II pneumocytes, lamellar bodies and lung lavages. In contrast, the turnover of surfactant cholesterol and surfactant lipids does not change. Hyperoxia caused an increase in vitamin E uptake by type II pneumocytes an enrichment of vitamin E in lamellar bodies.     

Phospholipid exchange between subcellular organelles of rabbit lung

A soluble protein fraction (PLEP) prepared from rabbit lung can catalyze the exchange of phospholipids between subcellular organelles of the lung and between these subcellular organelles and synthetic liposomes. Phospholipid exchange between microsomes and synthetic liposomes and between mitochondria and synthetic liposomes was stimulated 8-fold and 2.5-fold, respectively, in the presence of the protein fraction. Lung exchange protein could also catalyze phospholipid exchange between subcellular organelles of the liver and synthetic liposomes. Phospholipid transfer between microsomes and lamellar bodies of the lung was stimulated 2-fold by the exchange protein. Both radiolabeled phosphatidylcholine (PC) and phosphatidylinositol (PI) were transferred from³²P-labeled microsomes to lamellar bodies, but the exchange protein exhibited no transfer activity for phosphatidylglycerol (PG) and that for phosphatidylethanolamine (PE) was insignificant compared to the transfer activity for phosphatidylcholine and phosphatidylinositol. While the physiological role of the phospholipid exchange proteins in the lung is unknown, it is possible that they participate in the distribution of the newly synthesized phospholipids from the site of synthesis to lamellar bodies and other membrane compartments of cells.     

Lung lipid composition in zinc-deficient rats

There have been a limited number of studies investigating surfactant lipid changes in lung with trace elements. The present investigation was designed to examine the effect of moderate zinc deficiency on the lipid metabolism in rat lung. We also evaluated whether zinc deficiency, which is a wide-spread problem, could play a role in adult respiratory distress syndrome (ARDS). For that purpose, adult male Wistar rats were fed two diets differing in zinc concentration. The rats were divided into two groups. One group was fed a zinc-deficient diet containing 3 mg Zn/kg, and the other group received a zincadequate control diet with 30 mg Zn/kg according to AIN 93-M. After 2 mon of treatment, we observed that in the zinc-deficient group (i) total lipids, phospholipids, and cholesterol increased whereas TG decreased in whole lung; (ii) phospholipid (PC) concentration increased in lamellar bodies and alveolar macrophages and decreased in extracellular surfactant but did not change in microsomes; (iii) protein concentration decreased in whole lung, extracellular surfactant, lamellar bodies, and macrophages; (iv) the incorporation of [Me-¹⁴C]choline into PC (phospholipids) of lung slices increased; and (v) the activity of CTP/phosphocholine cytidylyltransferase bound to the microsomes increased in the lung. These results suggest that the lipid concentration in the lung (especially the phospholipids) is modified directly or indirectly by a zinc-deficient diet. In a zincdeficient diet, the lung changes the pattern of PC for an adaptive or recovery stage. Therefore, zinc deficiency implications are important for the design of therapies and public health interventions involving targeted zinc supplementation for high-risk groups or groups with certain diseases, such as ARDS.     

Ozone-induced alterations of lamellar body lipid and protein during alveolar injury and repair

Alveolar Type II cells in the rat respond to severe, acute ozone injury (3 ppm ozone for eight hours) by increasing their intracellular pool of surfactant; however, the newly stored surfactant is abnormal in composition. Lamellar bodies isolated between 24 and 96 hours after ozone exposure contained significantly more cholesterol in relation to phosphatidylcholine than did controls. By contrast, the cholesterol content of surfactant isolated from alveolar lavage remained unchanged throughout an 8-day post-ozone period. The total protein content of lamellar bodies in relation to phosphatidylcholine was significantly decreased at 24 and 48 hours post-ozone. Analysis of lamellar body proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the amount of a 14 kDa proteolipid was greatly reduced at the end of the eight-hour ozone exposure and remained low for at least 48 hours. This proteolipid appeared to be a specific lamellar body component since it was not detected in extracellular surfactant. The findings indicate that oxidative alveolar stress initiates characteristic alterations in both lipid and protein constituents of stored surfactant, without perturbation in the composition of extracellular surfactant.     

Subcellular distribution of disaturated phosphatidylcholine in developing rabbit lung

To determine the subcellular distribution of disaturated phosphatidylcholine (DSPC) in lung tissue during perinatal development, fetal rabbits at 24, 26, 28 and 31 (term) days gestation and newborns were studied. Following alveolar lavage, fractions enriched in nuclei-cellular debris, mitochondria, microsomes, surfactant (lamellar bodies) and cytosol were prepared from the residual tissue homogenate, and their DSPC content was determined. The DSPC content of the unfractionated residual lung tissue homogenate progressively and significantly increased during fetal development, rising from 9.09±0.91 to 17.45±2.88 mg/g dry lung between 24 days gestation, and term. Between 24 and 26 days gestation the overall increase in tissue DSPC was due to a two-fold increase in the mitochondrial, microsomal and cytosolic pools. Lamellar bodies were first isolable at 26 days gestation. The DSPC content of this fraction increased six-fold (from 0.10±0.02 to 0.67±0.15 mg/g dry lung) between 26 and 28 days gestation and a further seven-fold (to 4.63±1.06 mg/g dry lung) by term, accounting for the overall increase in the tissue homogenate value during this time period. By the first postnatal day, microsomal and cytosolic DSPC increased another two-fold, but no significant change occurred in the other subcellular fractions. Alveolar lavage DSPC progressively increased over the time period studied. While there was no change in the lamellar body DSPC/total PC ratio during fetal development, each of the mitochondrial, microsomal and cytosolic ratios decreased between days 26 and 28 of gestation and then increased at term. Our results indicate that in addition to the pulmonary surfactant, for which DSPC is often used as a marker, other subcellular organelles contain significant DSPC pools that undergo dynamic changes in size during perinatal development.     

Effect of hyperpnea on enzymes of the CDPcholine path for phosphatidylcholine synthesis in rat lung

We have examined the activity of three enzymes in pulmonary surfactant phosphatidylcholine synthesis following the hyperpnea induced by having rats either inspire 5% CO₂/13%O₂/82% N₂ for 24 hr or swim in thermoneutral water for 30 min. Both stimuli markedly increase frequency and tidal volume of breathing and promote the release of surfactant. Lungs were perfused to remove blood, lavaged, and then homogenized in 1 mM Hepes, 0.15M KCl at pH 7.0. The homogenate was centrifuged at 9,000 g (av) for 10 min to sediment the mitochondria and lamellar bodies and at 100,000 g (av) for 60 min to obtain the microsomal and cytosol fractions. Incubations were carried out under determined optimal conditions and zero order kinetics. Choline kinase (CK), cholinephosphate cytidylytransferase (CP-cyT) and choline phosphotransferase (CPT) were assayed by the incorporation of [methyl-¹⁴C] choline chloride into phosphocholine, [methyl-¹⁴C]phosphocholine into CDPcholine, and [¹⁴C]CDPcholine into phosphatidylcholine, respectively. The incubation products were separated by thin-layer chromatography. Whereas both forms of hyperpnea increased the activity of CP-cyT in the microsomal fraction, they had no effect on the activity of either cytosolic CP-cyT and CK, or microsomal CPT. A similar increase in tidal volume in an isolated perfused rat lung had no effect. We conclude that,in vivo, hyperpnea increases the activity of CP-cyT, the rate-limiting enzyme in phosphatidylcholine synthesis. Whether this is due to an increase in the amount of enzyme, or of a cofactor, is unknown.     

Source of lung surfactant phospholipids: Comparison of palmitate and acetate as precursors

The phospholipids and the fatty acid compositions of major phospholipids in rat lung parenchyma, microsomes, lamellar bodies and alveolar wash were quantified. Adult rats were injected simultaneously with [³H] palmitate and [¹⁴C] acetate into the femoral vein. The appearance of labeled phosphatidylcholine (PC), disaturated phosphatidylcholine (DSPC) and phosphatidylglycerol (PG) in each lung fraction was measured during short periods of time (5 min to 2 hr) after isotope administration. Relatively more PC, DSPC and PG labeled with acetate radioactivity in lung microsomes entered lamellar body and alveolar wash fractions than those labeled with palmitate radioactivity. However, there was no difference between palmitate and acetate labeled phospholipids in the transport from microsomes to lamellar bodies by phospholipid exchange proteins. On the other hand, prior injection of colchicine resulted in decrease in the transport of PC from microsomes to alveolar space to a relatively greater extent in the acetate radioactivity than in the palmitate radioactivity.     

Distribution of the phosphatidate phosphohydrolase activity in the lamellar body and lysosomal fractions of lung tissue

Phosphatidate phosphohydrolase (PAPase) activity was measured in lamellar bodies purified from porcine lung tissue. After repeated freeze-thawing, only a negligible amount of PAPase activity was released into the soluble fractions, whereas there was release of 2 lysosomal marker enzyme activities, glucosaminidase and β-galactosidase into the soluble fraction. In addition, a lysosomal-enriched fraction was prepared from adult rat lung tissue by prior treatment of the rats with Triton WR 1339. Treatment with Triton WR 1339 resulted in the significant shift of the activities of the lysosomal marker enzymes, glucosaminidase and β-galactosidase, to less dense subcellular fractions. The highest specific activity of PAPase was found in a subcellular fraction which had a density that was intermediate between that of the mitochondrial and microsomal fractions and the distribution of PAPase activity was not affected by the prior treatment of the rats with Triton WR 1339.     

Concentrated phases of an ionic surfactant (Aerosol OT) in polar solvents

We have studied concentrated phases of Aerosol OT (AOT) in polar (water, ethylene glycol, formamide, N,N-dimethylformamide) and apolar (isooctane) solvents. We investigated two surfactant volume fractions (φ = 0.2 and φ = 0.6) with small angle x-ray scattering (SAXS), rheology and electrical conductivity experiments. AOT self-assembles differently depending on solvent type and concentration. SAXS experiments show that the AOT/water system displays a lamellar phase. In the other cases, only formamide displays a lamellar phase for φ = 0.6. The other solvents (and formamide at φ = 0.2) promote the self-assembly of AOT in other microstructures. The SAXS spectra display correlation peaks consistent with a disordered array of cylindrical aggregates. The microstructure of the AOT/isooctane system at φ = 0.2 is that of an arrangement of spherical aggregates. The results are explained in terms of surfactant packing models and solvent properties. For instance, the ability of ethylene glycol to form hydrogen bonds with AOT promotes the formation of cylindrical aggregates by increasing the area per surfactant polar head. As N,N-dimethylformamide is slightly miscible in hydrocarbons it increases the volume of the surfactant tail promoting reverse structures.     

Influence of glycols on the formation of lamellar liquid crystals with an anionic surfactant,oleic acid,and water

The influence of glycol structures on the formation of lamellar liquid crystals with the physical appearance of transparent gels in formulations composed of an anionic surfactant, oleic acid, and water was investigated. The glycols studied belong to alkyl derivatives of ethylene glycol and diethylene glycol. The relationships between the ingredients of the so-called basic compositions—surfactant, oleic acid, and glycol—were optimized to form transparent gels when diluted with water. The ranges in which transparent gels existed were compared for the systems with different glycols. The most suitable glycols, as defined by the lowest surfactant content in the final transparent gels, were ethylene glycol methyl ether and especially methyl and ethyl derivatives of diethylene glycol. Formulations with 2–3% surfactant could be prepared with these glycols. These data were correlated with the polarity of the glycol structures described by means of log P (octanol/water partition coefficient). Transparent gel formation occurred for log P values ranging from approximately 0.5 to −0.5, whereas liquid crystal formation did not result from higher or lower values.     

Self‐Aggregation and Emulsifying Properties of Methyl Ester Sulfonate Surfactants

Methyl ester sulfonate (MES) anionic surfactants made from natural resources are of particular interest as sustainable surfactants. They offer good physicochemical properties for applications as detergents and emulsifiers. The liquid crystal structures of MES surfactants synthesized in a previous work were determined by polarizing optical microscopy (POM) and small‐angle X‐ray scattering (SAXS). The emulsifying activity for each surfactant was also measured, and the stability of emulsions was estimated and compared to that induced by sodium dodecyl sulfate (SDS). The POM micrographs showed the presence of birefringent textures. Several factors, including temperature and hydration, influenced the stability of the phases and their structure. SAXS confirmed the structure of the phases formed by dry and hydrated ф‐MES surfactants at 25 °C, giving the position of peaks corresponding to the ratio 1:2:3 and revealing the phase transitions of lamellar to double lamellar or the reverse. Also, the Bragg distance (d) decreased with an increase in chain length from 13 to 17 carbon atoms and an increase in the area per molecule of surfactant. The geometric packing parameters were also determined, and suggest that surfactants are tilted. The stability of surfactant emulsions is around 60%, which is comparable to that of SDS. The micrographs show that the emulsions formed are O/W, and an increase in chain length gives rise to a decrease in the size of the emulsion droplets. These results are confirmed by the values of hydrophilic‐lipophilic balance (HLB) which reveals the hydrophilic nature of these surfactants.     

Synthesis,stability, and biodegradability studies of a surface-active amide

A homolog pure nonionic surfactant, tetra(ethylene glycol) mono-n-octaneamide, was synthesized. The surfactant was characterized by determining the critical micelle concentration, cloud point, and biodegradation. Hydrolysis catalyzed by an acid, an alkali, a peroxide, and enzymes [peptidase from porcine, amidase from Pseudomonas aeruginosa, and two lipases, Mucor miehei lipase (MML) and Candida antarctica lipase B (CALB)] was investigated using ¹H nuclear magnetic resonance. The surfactant was stable toward the acid, alkali, and peroxide. When subjected to peptidase and CALB, the amide was cleaved, although at a low rate. No reaction was obtained when using the amidase or MML. The biodegradation test resulted in more than 60% degradation after 28 d. Based on these results, the amide surfactant can be considered chemically stable, yet highly biodegradable, which generally is an ideal combination of properties for a surfactant.     

Synthesis of platelet activating factor by cholinephospho-transferase in developing fetal rabbit lung

Developing fetal lung is a possible source of the platelet activating factor (PAF, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) present in amniotic fluid of women in labor. We have assayed the microsomal activities of a specific enzyme for the de novo synthesis of PAF in developing fetal and neonatal rabbit lung, 1-alkyl-2-acetyl-glycerol-dependent dithiothreitol-insensitive cholinephosphotransferase. The specific activity of this enzyme increased from 0.92 to 3.60 nmol×min⁻¹×mg⁻¹ protein between day 21 and day 31 of gestation. In contrast, during this same period the activity of the PAF-biosynthetic cholinephos-photransferase in developing rabbit kidney did not change significantly. The specific activity of the diacyl-glycerol-dependent, dithiothreitol-sensitive cholinephos-photransferase that catalyzes the final step in phosphatidylcholine biosynthesis was not altered during late gestation in either fetal lung or kidney. Previously, increased amounts of pulmonary PAF had been found during the latter stages of gestation (Hoffman, Truong and Johnston (1986)Biochim. Biophys. Acta 879, 88–96) and may be attributed to increased activity of the PAF biosynthetic enzymes found in this investigation. This elevated level of PAF in fetal lung may serve to facilitate breakdown of glycogen that provides, in part, the carbon and energy source for surfactant biosynthesis. In addition, PAF may be secreted in association with surfactant into amniotic fluid in which it may interact with amnion tissue and subsequently participate in the events associated with the initiation of parturition.     

A Concise Review on Nano-emulsion Formation by the Phase Inversion Composition (PIC) Method

Nano-emulsion formation by the phase inversion composition method is reviewed. The relationship between phase behavior and nano-emulsion formation is revised with emphasis on the key role of phase transitions involving changes in the sign of the curvature of the surfactant layer (inversion) via zero-average-curvature structures such as bicontinuous microemulsions or lamellar liquid crystalline phases. The different low-energy methods that can be involved in a nano-emulsification process at constant temperature are also discussed.     

Lamellar silica mesostructures assembled from a new class of Gemini surfactants: alkyloxypropyl-1,3-diaminopropanes

Abstract  

Representative members of a new class of commercially available Gemini surfactants, namely, the alkyloxypropyl-1,3-diaminopropanes, are shown to template the direct assembly of mesoporous silicas with lamellar framework structures. The hydrolysis of tetraethylorthosilicate in the presence of a derivative with a straight hydrophobic chain, C _n H_2n+1O(CH₂)₃NH(CH₂)₃NH₂ with n = 8 and 10 (Tomah3 DA1214), afforded a layered mesophase with a surface area of 464 m²/g, a pore volume of 0.39 cm³/g, a pore size of 3.6 nm and a vesicular hierarchical structure. The introduction of electrostatic forces into the assembly process through the protonation of up to 33% of the amine centers improves the quality of the lamellar framework order as evidenced by increases in X-ray diffraction and textural properties. Also, the vesicular hierarchical structure formed under electrically neutral assembly conditions is replaced by well dispersed multilamellar nanoparticles upon surfactant protonation. Chain branching in the hydrophobic segment of Gemini derivative i-C₁₀H₂₁O(CH₂)₃NH(CH₂)₃NH₂ (Tomah3 DA14) compromises the quality of the lamellar framework structure, but affords higly dispersed nanoparticles with hierarchical coiled slab to vesicular motifs depending on the degree of surfactant protonation. In addition to providing unusual lamellar framework structures, these Gemini surfactants afford hierarchical nanoparticle motifs of relatively uniform size (50–200 nm) and a very high degree of dispersion for a potential use in a variety of materials applications.     

Effects of cationic liposome-DNA complexes on pulmonary surfactant function in vitro and in vivo

Cationic liposome-DNA complexes are being evaluated as potential gene therapy agents for the lung. Cations have strong effects on the biophysical functions of lung surfactant. Therefore, we assessed whether cationic liposomes [composed of N-(1-(2,3-dioleyloxy) propyl)-N,N,N-trimethyl-ammonium chloride and dioleylphosphatidylethanolamine] with or without DNA affect behavior of four types of surfactant in vitro. Experiments were carried out using a modified Wilhelmy surface balance. The ability of surfactants that contain protein and anionic lipids to lower surface tension was inhibited in the presence of cationic liposomes. Inactivation was less when DNA was preincubated with cationic liposomes. Surfactant that contained neither protein nor anionic lipids was not inactivated. Mechanical properties of the lung were studied to assess in vivo surfactant function after intratracheal instillation of a cationic liposome-DNA complex into adult rats. Pressure-volume deflation curves were shifted by 18% compared with those from normal (untreated) animals, but this effect was transient and not different from that observed in animals who received a similar volume of saline. These findings indicate that cationic liposomes alone may have deleterious effects on behavior of some surfactants possibly by disrupting charge interactions between negatively charged phospholipids and surfactant proteins. When DNA is added to liposomes before exposure to surfactants, the adverse charge interactions may be obviated by charge neutralization of liposomes by DNA.