alveolar surfactant

Definition: Pulmonary surfactant is a phospholipid-protein complex that serves to lower the surface tension at the air-liquid interface in the alveoli of the lung. It is essential to normal respiration.

Pulmonary surfactant is a surface-active lipoprotein complex formed by type II alveolar cells (type 2 pneumocytes). The proteins and lipids that comprise surfactant have both a hydrophilic region and a hydrophobic region.

By adsorbing to the air-water interface of alveoli with the hydrophilic headgroups in the water and the hydrophobic tails facing towards the air, the main lipid component of surfactant, dipalmitoylphosphatidylcholine, reduces surface tension.

Pulmonary surfactant is composed primarily of dipalmitoylphosphatidylcholine and 2 major protein species of relative molecular weights 32,000 and 10,000.

Composition

 Lipids of the surfactant

Over 90% of the surfactant is lipids.

Around half of which is dipalmitoylphosphatidylcholine (DPPC). This is a phospholipid with two 16-carbon saturated chains and a phosphate group with quaternary amine group attached.

Phosphatidylcholine molecules form 85% of the lipid in surfactant and have saturated acyl chains. Phosphatidylglycerol (PG) forms about 11% of the lipids in surfactant, it has unsaturated fatty acid chains that fluidize the lipid monolayer at the interface.

Neutral lipids and cholesterol are also present. The components for these lipids diffuse from the blood into type II alveolar cells (type 2 pneumocytes) where they are assembled and packaged for secretion into secretory organelles called lamellar bodies.

 Proteins of the surfactant

Proteins make up the remaining 10% of surfactant. Half of this 10% is plasma proteins but the rest is formed by the apoproteins SP-A (SFTPA1), B (SFTPB), C (SFTPC) and D (SFTPD). (SP standing for "surfactant protein".)

SP-A and SP-D confer innate immunity as they have carbohydrate recognition domains that allow them to coat bacteria and viruses promoting phagocytosis by macrophages. SP-A is also thought to be involved in a negative feedback mechanism to control the production of surfactant.

SP-B and SP-C are hydrophobic membrane proteins that increase the rate that surfactant spreads over the surface. SP-B and SP-C are required for proper biophysical function of the lung. Humans and animals born with a congenital absence of SP-B suffer from intractable respiratory failure whereas those born lacking SP-C tend to develop progressive interstitial pneumonitis.

The apoproteins are produced by the secretory pathway in type 2 pneumocytes. They undergo much post-translational modification, ending up in the lamellar bodies. These are concentric rings of lipid and protein, about 1 µm in diameter.

Production

Surfactant production in humans begins in type 2 pneumocytes during the terminal sac stage of lung development.

Lamellar bodies appear in the cytoplasm of type 2 pneumocytes at about 20 weeks gestation. These lamellar bodies are secreted by exocytosis into the surface water layer lining the alveolar airspace, where the surfactant forms a meshwork of tubular myelin.

Term infants are estimated to have an alveolar storage pool of approximately 100mg/kg of surfactant, while preterm infants have an estimated 4-5mg/kg at birth.

Recycling

This alveolar surfactant can be both broken down by macrophages and/or reabsorbed into the lamellar structures of type II cells. Up to 90% of surfactant phosphatidylcholine is recycled from the alveolar space in the newborn.

Clara cells also produce a component of lung surfactant.

Pathology (surfactant anomalies)

Inadequate amounts of surfactant at birth, a frequent situation in premature infants, results in respiratory failure.

 congenital surfactant deficiency (CSD)

• mutations of surfactant proteins
  • SP-A deficiency
  • SP-B deficiency
  • SP-C deficiency

 deficiency of lamellar bodies in alveolar type II cells with normal surfactant protein (10673207)

See also

 surfactants

References

 Alveolar Surfactant Homeostasis and the Pathogenesis of Pulmonary Disease. Whitsett JA, Wert SE, Weaver TE. Annu Rev Med. 2009 Oct 7. PMID: 19824815

 Whitsett JA, Weaver TE. Hydrophobic surfactant proteins in lung function and disease. N Engl J Med. 2002 Dec 26;347(26):2141-8. PMID: 12501227

 Devendra G, Spragg RG. Lung surfactant in subacute pulmonary disease. Respir Res. 2002;3(1):19. PMID: 11980588

 Rooney SA, Young SL, Mendelson CR. Molecular and cellular processing of lung surfactant. FASEB J. 1994 Sep;8(12):957-67. PMID: 8088461