The effect of elevated dietary cholesterol on pulmonary surfactant function in adolescent mice

Abstract

It has been established that phospholipids and cholesterol interact in films of pulmonary surfactant (PS). Generally it is thought that phospholipids increase film stability whereas cholesterol increases film fluidity. To study this further, we modified dietary cholesterol in mice which received either standard rodent lacking cholesterol (sd), or high cholesterol (2%) diet (hc) for 1 month. Phospholipid stability was investigated by a capillary surfactometer (CS), which measures airflow resistance and patency. PS was collected by bronchiolar lavage and centrifuged to obtain the surface-active film (SAF). Results showed that the hc-SAF had significantly more cholesterol than sd-SAF. CS analyses at 37 degrees C showed no significance differences in airflow resistance between hc-SAF and sd-SAF. However, at 37 degrees C, sd-SAF showed greater ability to maintain patency compared to hc-SAF, whereas at 42 degrees C hc-SAF showed patency ability similar to sd-SAF. The results suggested that increased cholesterol in hc-SAF induced less stability in the SAF possibly due to cholesterol's fluidizing effect on phospholipids at physiological temperatures.

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

“…Cholesterol from serum lipoproteins is taken up by the type II cell and incorporated into the surfactant before secretion (15). Furthermore, it has recently been demonstrated that mice fed a high cholesterol diet exhibit an increased level of serum cholesterol and that the surfactant obtained from these mice had increased cholesterol values with impaired biophysical function (24). However, Davidson et al (7) demonstrated that lowering levels of serum cholesterol by inhibiting the release of hepatic lipoproteins did not affect surfactant cholesterol levels, due to the ability of type II cells to synthesize cholesterol.…”

Decreased serum level of lipoprotein cholesterol is a poor prognostic factor for patients with severe community-acquired pneumonia that required intensive care unit admission

“…High-density lipoprotein cholesterol serves a unique function in normal lung physiology [26][27][28]. Recent studies have revealed important roles for cholesterol regulators on pulmonary immune responses to the lung injury and infection [29][30][31][32].…”

The effect of diet-induced serum hypercholesterolemia on the surfactant system and the development of lung injury

“…This finding was somewhat surprising in light of an earlier study conducted by McCrae and colleagues which examined the surfactant system from adolescent female mice fed a high-cholesterol diet [29]. These mice had a significant increase in both their serum cholesterol levels and the amount of cholesterol in their surfactant without marked changes to their lamellar body content or lipid droplets in the lipofibroblast [29]. Furthermore, assessment of surfactant biophysical function using a capillary surfactometer demonstrated decreased airway patency and reduced surface film activity in hypercholesterolemic mice.…”

“…It is possible that the lungs respond to such a condition through a compensatory mechanism involving lipid storage in pulmonary lipofibroblasts [29] with potential impact on surfactant only in a more chronic condition. A limitation of our study therefore, was that the onset of their hypercholesterolemia was acute and does not represent the human development of the condition due to chronic ingestion of high-fat and high-cholesterol foods.…”