Effect of serum, cholesterol and low density lipoprotein on the functionality and structure of lung surfactant films.

Lung surfactant is a complex mixture of lipid and protein, responsible for alveolar stability, becomes dysfunctional due to alteration of its structure and function by leaked serum materials in disease. Serum proteins, cholesterol and low density lipoprotein (LDL) were studied with bovine lipid extract surfactant (BLES) using Langmuir films, and bilayer dispersions using Raman spectroscopy. While small amount of cholesterol (10 wt%) and LDL did not significantly affect the adsorption and surface tension lowering properties of BLES. However serum lipids, whole serum as well as higher amounts of cholesterol, and LDL dramatically altered the surface properties of BLES films, as well as gel-fluid structures formed in such films observed using atomic force microscopy (AFM). Raman-spectroscopic studies revealed that serum proteins, LDL and excess cholesterol had fluidizing effects on BLES bilayers dispersion, monitored from the changes in hydrocarbon vibrational modes during gel-fluid thermal phase transitions. This study clearly suggests that patho-physiological amounts of serum lipids (and not proteins) significantly alter the molecular arrangement of surfactant in films and bilayers, and can be used to model lung disease.

Interactions of serum with lung surfactant extract in the bronchiolar and alveolar airway models.

Lung surfactant (LS) a lipid-protein mixture is secreted by type-II pneumocytes and prevents alveolar collapse as well as maintains upper airway patency. In certain lung pathophysiology dysfunction of the LS occurs due to leakage of serum derived materials interacting with surfactant at the respiratory air-water interface. Bovine lipid extract surfactant (BLES) with and without foetal calf serum (FCS) were studied as models of bronchiolar airway patency using a capillary surfactometer, and in alveolar (terminal) airway using adsorbed Langmuir films in a surface balance. About 5 wt.% of serum was found to maximally decrease airway patency of BLES by 90%, as well as the surface films ability to reach low surface tension below 25 mN/m. In fact, FCS was found to be about 200-fold more potent inhibitor of the surfactant extract compared to a major serum component, albumin. Also serum but not albumin significantly reduced the gel-phase structures found in BLES films under compression at low amounts (5-10 wt.%), and eventually abolished these organized structures as imaged by fluorescence and atomic force microscopy. This fact suggests that serum caused complete molecular re-organization of the surfactant lipids in films at an air-water interface, and the ability of such films to reduce surface tension or maintain airway patency. The study may provide a novel structure-function disruption model for lung surfactant inactivation in the airways in pathophysiology.