PHOSPHATIDYL CHOLINE AS LUNGS SURFACTANT


The surfactants are the chemical substance that is capable of lowering surface tension. The lung surfactants contain a complex mixture of phospholipids, neutral lipids, and specific proteins. The lung surfactants are essential for normal lung function as it reduces surface tension at the air-liquid interface of alveolar spaces. Phosphatidylcholine is the major component of the surfactant comprising 90% of the lipids. Four specific surfactant proteins SP-A, SP-B, SP-C, SP-D. The synthesis and secretion of functional surfactants are confined to type II cells of the alveolar epithelium.

The fundamental pathway for lung surfactant phospholipid synthesis, it's packaging into storage lamellar bodies (LB), secretion into the alveolar lining fluid and recycling back into ATII cells are well known. Bulk surfactant phospholipid synthesized at the ER is transported to LBs by a mechanism that may employ specific carrier proteins and/or traffic through the Golgi. During the processes of synthesis, transport, and selection, the PC components are enriched saturated species that involves
a) the combination of acyl remodeling of unsaturated species,
b) selective transport of saturated species or selective exclusion of unsaturated species.

Newly synthesized surfactant, in the apical membrane (LBs), then adsorbs to the air-liquid interface where saturated PC contributes to surface activity.

Infant respiratory distress syndrome:
The developmental insufficiency of these surfactants production and immature structural immaturity of lungs in neonates leads to a pathological condition known as Infant respiratory distress syndrome. For the prenatal diagnosis, the fetal lung maturity may be tested by sampling the amount of surfactant in the amniotic fluid by amniocentesis. Several tests are available that correlate with the production of surfactant.
Example- Lecithin-sphingomyelin ratio ("L/S ratio"): If the result is less than 2:1, the fetal lungs may be surfactant deficient. The presence of PG usually indicates fetal lung maturity.

History on the identification of Lungs surfactant
Van Neegard first hypothesized that lungs consist of an active substance that exerts and maintain a low alveolar surface tension, allows adequate ventilation of the peripheral airways for normal lungs function, and prevent end-expiratory alveolar collapse. It was strongly believed that these surfactants are lipoproteins- a mixture of phospholipids and proteins. Based on the results obtained from centrifugations and recovery of phospholipids and proteins from lungs washing and homogenates, the composition of lipids and protein were not uniform across the experiments. There was certainly two possibilities:
a) Lung surfactant constitutes large lipoproteins component,
b) Phospholipids are the major lung surfactant and proteins are only artifacts.

Because of uncertainty that if phospholipids are the integral component of large lipoprotein complex or entirely independent entity that function as lung surfactant, researchers have used analysis of protein and lipid mixture obtained from the lung sample, ultracentrifugation to find the fraction of lipoproteins. The research findings concluded that phospholipids are a major component of lung surfactant and a small fraction of proteins function to reduce surface tension in the lungs.