Surface Properties Of Surfactant Research Articles

In vitro inhibition of biophysical surface properties and change in ultrastructures of exogenous pulmonary surfactant by albumin or fibrinogen.

In order to observe the effects of serum albumin and fibrinogen on biophysical surface properties and the morphology of pulmonary surfactant in vitro, we measured the surface adsorption rate, dynamic minimum and maximum surface tension (min-, max-ST) by Pulsating Bubble Surfactometer, and demonstrated ultrastructures on a series of mixtures with varying concentrations of albumin or fibrinogen and Surfactant-TA. The albumin and fibrinogen significantly inhibited the adsorption rate and ST-lowering properties of surfactant through increasing STs of adsorption rate, min-ST, and max-ST. The characteristic morphology of the Surfactant-TA changed from lamellar rod-like structure with open ends into spherical structures with loss of their open ends by mixing with albumin or fibrinogen. These inhibitory effects of albumin and fibrinogen on surface properties of surfactant were dependent upon the increasing concentration of albumin or fibrinogen. We concluded that albumin and fibrinogen significantly altered surfactant function and its ultrastructural morphology in vitro. These findings support the concept that albumin and fibrinogen-induced surfactant dysfunction may play an important role in the pathophysiology of adult respiratory distress syndrome, and this adverse effect of albumin and fibrinogen on surfactant might be overcome by administration of large doses of exogenous surfactant.

Inhaled nitric oxide injures the pulmonary surfactant system of lambs in vivo.

Nitric oxide (.NO) is a free radical, and as such may damage the pulmonary surfactant system. To determine the potential toxicity of .NO in vivo, we exposed 35 newborn lambs to 0, 20, 80 or 200 ppm .NO in either 21 or 60% O2 for 6 h. At the end of the exposure, lambs had normal values of arterial Po2, Pco2, and pH; total protein concentration in the bronchoalveolar lavage was also at normal levels. There were no differences in the surface properties of surfactant among the air or 60% O2 groups. Pulmonary surfactant samples, isolated from the bronchoalveolar lavage of lambs breathing air or 20 ppm .NO and reconstituted at a lipid concentration of 3 mg/ml, reached a low minimum surface tension (Tmin < 3 mN/m) in a pulsating bubble surfactometer. On the other hand, abnormal surface properties were observed in 36 and 60% of surfactant samples isolated from lungs of lambs that breathed 80 or 200 ppm .NO, respectively. These findings were confirmed using a captive bubble surfactometer. Surfactant protein A, isolated from the lungs of lambs that breathed 200 ppm .NO, exhibited decreased ability to aggregate lipids in vitro. These data are consistent with injury to the surfactant apoproteins during inhalation of either 80 or 200 ppm .NO for 6 h.

Alterations in surfactant protein gene expression associated with premature birth and exposure to hyperoxia

Steady-state levels of mRNAs for the three surfactant-associated proteins, SP-A, SP-B, and SP-C, were measured in a primate model of premature birth and survival. These values were determined by Northern and quantitative slot blot analyses of total lung RNA during both in utero and extrauterine development of the fetus as well as in response to hyperoxic exposure. The composition and surface properties of surfactant were also analyzed to determine the effect of differential expression of the surfactant proteins on the overall composition and function of surfactant. The data clearly demonstrate that the regulation of surfactant mRNA levels in the premature fetus is under complex physiological control. Interruption of in utero development by premature birth results in increased levels of all three surfactant mRNAs, presumably in response to precocious initiation of air breathing. Within the first 24 h after parturition both SP-B and SP-C mRNA levels are increased beyond the levels found in the full-term fetal controls. Expression of mRNA for these genes peaks on day 2 and thereafter drops to levels below that found on day 1. However, response of the SP-A gene to premature birth is slow and transcripts from this gene lag considerably behind values found in the full-term fetus. Furthermore, exposure of the premature fetus to hyperoxia results in an increase in the steady-state levels of SP-B and SP-C mRNA without significant changes in SP-A. Defects in the ability of the SP-A gene to respond to extrauterine exposure and hyperoxia may be contributing to development of bronchopulmonary dysplasia, a common clinical complication of premature birth in humans.

Rapid Clearance of Surfactant-Associated Palmitic Acid from the Lungs of Developing and Adult Animals

Palmitic acid is a minor component of natural surfactant and has been used to modify lipid extracts of natural surfactants to optimize their in vitro surface properties. The metabolic fate of palmitic acid in surfactant is unknown. The clearance of surfactant-associated radiolabeled palmitic acid after intratracheal administration was investigated with trace doses of surfactant in the adult rabbit and with trace and treatment doses in the 28-d fetal rabbit and the 132-d fetal sheep. Palmitic acid was cleared rapidly from the airways, with less than 2% of the radiolabel recovered as free palmitic acid in the alveolar wash by 1 h in all models. Recovery as free palmitic acid in the total lung at 2 h was 2% in the adult rabbit and 3% both doses in the preterm rabbit. In the preterm sheep, the recovery as free palmitic acid in the total lung was approximately 2% of the trace dose and 1% of the treatment dose by 5 h. Between 5 and 15% of the instilled palmitic acid was used as substrate for phospholipid synthesis by the lung in the different models. About 30% of the palmitate derived label was recovered in lipid extracts of liver 30 min after tracheal instillation of labeled surfactant in adult rabbits, whereas only 5-10% of the palmitate derived label was found in liver lipids in the preterm animals. In contrast to palmitic acid, radiolabeled triglyceride was cleared much more slowly from the airspaces and lungs of preterm sheep. Inasmuch as large amounts of palmitic acid are cleared rapidly from airspaces and lung tissue, it will not have a prolonged effect on the surface properties of surfactant but it may serve as a precursor for lung lipid metabolism.

Lung lipids and disease.

Pulmonary surfactant is a complex mixture of proteins and phospholipids which possesses unique physical properties. It is no longer viewed just as a system for lowering surface tension but may play a protective role particularly with reference to inhalation of noxious substances. Derangement of the surfactant system may proceed to the development of disease by opening the way to toxic injury of the delicate epithelial lining of the lungs. Currently, it is believed that surfactant, which is synthetised, stored and secreted by type II alveolar pneumocytes, spreads rapidly on release to form a monomolecular layer covering the squamous surface lining of the alveoli. Furthermore, physiological and histological studies show that this monolayer extends into the bronchioli and possibly bronchi also. Effectively, the inspired air encounters an extensive and continuous 'oily' surface. It has been known for some time that cigarette smokers appear to sequester pulmonary surfactant into alveolar macrophages, leaving less free surfactant on the alveolar and bronchiolar surfaces. This process may be initiated by physical inactivation of surfactant by tobacco smoke. The tar of tobacco smoke alters the surface properties of surfactant as well as the compliance of the lung in vitro. This process may not only lead to the associated increase in the number of alveolar macrophages found in smokers, but could, by lessening the effective protective role of surfactant, lead to direct toxic injury of the lung and the development of chronic obstructive lung disease.

The behaviour of lung surfactant in electrolyte solutions

Surface and electrokinetic properties of purified calf lung surfactant in various electrolyte solutions were determined. Surface properties were pH dependent in distilled water and the surfactant performed as a good lung surfactant only below pH 4. In more physiological media it was pH insensitive over the range 2–8.5. In distilled water at pH 6 its surface properties improved when NaCl was added up to 20 mM; above this concentration it had the surface properties required to stabilise alveoli. The surface properties of surfactant in distilled water were also restored by certain cations (Ca 2+, Mg 2+, Mn 2+, Cd 2+ and Ni 2+) but not others (Na +, K +, La 3+ and Fe 3+) when added to an ionic strength of 5.6 mM. Cations that restored its surface activity also reduced the surface charge density on the surfactant particles. Aggregation of surfactant by various metal chlorides was studied by light scattering measurements and bore no relation to surface activity or the charge on the particles. Aggregation of surfactant particles by Ca 2+, Cd 2+ and Mn 2+ was instantly reversed by addition of excess EGTA. The influence of electrolytes on the surface properties of lung surfactant is explained in terms of the electrostatic forces operating in the system.