Pulmonary surfactant function is abolished by an elevated proportion of cholesterol

Area of Science:

• Pulmonary physiology
• Biochemistry
• Medical research

Background:

• Pulmonary surfactant reduces surface tension at the lung epithelium-air interface.
• Human surfactant contains 5-10% cholesterol; elevated levels are found in acutely injured lungs (ALI).
• Cholesterol's role in surfactant function is controversial, with clinical formulations often excluding it due to in vitro studies suggesting impaired surface activity.

Purpose of the Study:

• To re-evaluate the functional role of cholesterol in pulmonary surfactant using an improved in vitro method.
• To assess the impact of varying cholesterol concentrations on the surface activity of a clinical surfactant formulation.

Main Methods:

• Utilized the captive bubble surfactometer (CBS) for in vitro evaluation of surfactant surface activity.
• Added varying percentages of cholesterol (0%, 5%, 10%, 20%) to bovine lipid extract surfactant (BLES).
• Assessed adsorption rate, minimum surface tension achieved, and area compression required for low surface tension.

Main Results:

• No significant differences in minimal surface tension were observed for BLES with 0%, 5%, or 10% cholesterol.
• These findings challenge previous studies suggesting deleterious effects of physiological cholesterol levels.
• At 20% cholesterol, surfactant function was abolished, preventing surface tension below 15 mN/m.

Conclusions:

• The detrimental effects of physiological cholesterol levels on surfactant function may be methodology-dependent.
• High cholesterol concentrations (20%) significantly inhibit surfactant activity, potentially contributing to impaired lung function in ALI.
• A molecular mechanism is proposed to explain cholesterol's differential effects at physiological versus high concentrations.