Pulmonary surfactant - Wikipedia, the free encyclopedia

6/28/15, 0:14

Pulmonary surfactant
From Wikipedia, the free encyclopedia

Pulmonary surfactant is a surface-active lipoprotein

complex (phospholipoprotein) formed by type II alveolar
cells. The proteins and lipids that make up the surfactant
have both hydrophilic and hydrophobic regions. By
adsorbing to the air-water interface of alveoli hydrophilic
head groups in the water and the hydrophobic tails facing
towards the air, the main lipid component of surfactant,
dipalmitoylphosphatidylcholine (DPPC), reduces surface
tension.

Contents
1 Function
1.1 Compliance
1.2 Alveolar size regulation
1.3 Prevent fluid accumulation and keep
airways dry
1.4 Innate immunity
2 Composition
2.1 Lipids
2.1.1 DPPC
2.1.2 Other phospholipids
2.2 Proteins
3 Artificial surfactants
4 Surface tension magnitude inside the lung
5 Production and Degradation
6 Diseases
7 History
8 References
9 External links

Diagram of the alveoli with both cross-section and

external view

Function
To increase pulmonary compliance.
To prevent atelectasis (collapse of the lung) at the end of expiration.
To facilitate recruitment of collapsed airways.
Alveoli can be compared to gas in water, as the alveoli are wet and surround a central air space. The surface
tension acts at the air-water interface and tends to make the bubble smaller (by decreasing the surface area of
the interface). The gas pressure (P) needed to keep equilibrium between the collapsing force of surface tension
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() and the expanding force of gas in an alveolus of radius r is expressed by the law of Laplace:

Compliance
Compliance is the ability of lungs and thorax to expand. Lung compliance is defined as the volume change per
unit of pressure change across the lung. Measurements of lung volume obtained during the controlled
inflation/deflation of a normal lung show that the volumes obtained during deflation exceed those during
inflation, at a given pressure. This difference in inflation and deflation volumes at a given pressure is called
hysteresis and is due to the air-water surface tension that occurs at the beginning of inflation. However,
surfactant decreases the alveolar surface tension, as seen in cases of premature infants suffering from infant
respiratory distress syndrome. The normal surface tension for water is 70 dyn/cm (70 mN/m) and in the lungs it
is 25 dyn/cm (25 mN/m); however, at the end of the expiration, compressed surfactant phospholipid molecules
decrease the surface tension to very low, near-zero levels. Pulmonary surfactant thus greatly reduces surface
tension, increasing compliance allowing the lung to inflate much more easily, thereby reducing the work of
breathing. It reduces the pressure difference needed to allow the lung to inflate. The lung's compliance decreases
and ventilation decreases when lung tissue becomes diseased and fibrotic.[1]

Alveolar size regulation

As the alveoli increase in size, the surfactant becomes more spread out over the surface of the liquid. This
increases surface tension effectively slowing the rate of expansion of the alveoli. This also helps all alveoli in
the lungs expand at the same rate, as one that expands more quickly will experience a large rise in surface
tension slowing its rate of expansion. It also means the rate of shrinking is more regular, as if one reduces in
size more quickly the surface tension will reduce more, so other alveoli can contract more easily than it can.
Surfactants reduce surface tension more readily when the alveoli is smaller because surfactants are more
concentrated.

Prevent fluid accumulation and keep airways dry

Surface tension forces also draw fluid from capillaries to the alveolar spaces. Surfactant reduces fluid
accumulation and keeps the airways dry by reducing these forces.[2]

Innate immunity
Surfactant immune function is primarily attributed to two proteins: SP-A and SP-D. These proteins can bind to
sugars on the surface of pathogens and thereby opsonize them for uptake by phagocytes. It also regulates
inflammatory responses and interacts with the adaptive immune response. Surfactant degradation or inactivation
may contribute to enhanced susceptibility to lung inflammation and infection.[3]

Composition
~40% dipalmitoylphosphatidylcholine (DPPC);
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~40% other phospholipids (PC);

~5% surfactant-associated proteins (SP-A, B, C and D);
Cholesterol (neutral lipids);
Traces of other substances.

Lipids
DPPC
This is a phospholipid with two 16-carbon saturated chains and a phosphate group with quaternary amine group
attached. The DPPC is the strongest surfactant molecule in the pulmonary surfactant mixture. It also has higher
compaction capacity than the other phospholipids, because the apolar tail is less bent. Nevertheless, without the
other substances of the pulmonary surfactant mixture, the DPPC's adsorption kinetics is very slow. This happens
primarily because the phase transition temperature between gel to liquid crystal of pure DPPC is 41 C, which is
higher than the human body's temperature of 37 C.
Other phospholipids
Phosphatidylcholine molecules form ~85% of the lipid in surfactant and have saturated acyl chains.
Phosphatidylglycerol (PG) forms about 11% of the lipids in the 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 where they are assembled and packaged for
secretion into secretory organelles called lamellar bodies.

Proteins
Proteins make up the remaining 10% of the surfactant. Half of this 10% is plasma proteins but the rest is formed
by the apolipoproteins SP-A (SFTPA1 (http://www.genenames.org/data/hgnc_data.php?match=SFTPA1)), B
(SFTPB (http://www.genenames.org/data/hgnc_data.php?match=SFTPB)), C (SFTPC
(http://www.genenames.org/data/hgnc_data.php?match=SFTPC)) and D (SFTPD
(http://www.genenames.org/data/hgnc_data.php?match=SFTPD)) (SP standing for "surfactant-associated
protein"). The apolipoproteins are produced by the secretory pathway in type II cells. They undergo much posttranslational modification, ending up in the lamellar bodies. These are concentric rings of lipid and protein,
about 1 m in diameter.
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 SP proteins reduce the critical temperature of DPPC's phase transition to a value lower than 37 C,[4] what
improves its adsorption and interface spreading velocity.[5][6] The compression of the interface causes a phase
change of the surfactant molecules to liquid-gel or even gel-solid. The fast adsorption velocity is necessary to
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maintain the integrity of the gas exchange region of the lungs.

Each SP protein has distinct functions, which act synergetically to keep an interface rich in DPPC during lung's
expansion and contraction. Changes in the surfactant mixture composition alter the pressure and temperature
conditions for phase changes and the phospholipids' crystal shape as well.[7] Only the liquid phase can freely
spread on the surface to form a monolayer. Nevertheless, it has been observed that if a lung region is abruptly
expanded the floating crystals crack like "icebergs". Then the SP proteins selectively attract more DPPC to the
interface than other phospholipids or cholesterol, whose surfactant properties are worse than DPPC's. The SP
also fastens the DPPC on the interface to prevent the DPPC from being squeezed out when the surface area
decreases [6] This also reduces the interface compressibility.[8]

Artificial surfactants
Synthetic pulmonary surfactants
1. Colfosceril palmitate (Exosurf) - a mixture of DPPC with
hexadecanol and tyloxapol added as spreading agents
2. Pumactant (Artificial Lung Expanding Compound or ALEC) - a
mixture of DPPC and PG
3. KL-4 - composed of DPPC, palmitoyl-oleoyl phosphatidylglycerol,
and palmitic acid, combined with a 21 amino acid synthetic peptide
that mimics the structural characteristics of SP-B.
4. Venticute - DPPC, PG, palmitic acid and recombinant SP-C
Animal derived surfactants
1. Beractant
1. (Alveofact) - extracted from cow lung lavage fluid
2. (Survanta) - extracted from minced cow lung with additional
DPPC, palmitic acid and tripalmitin
2. Calfactant (Infasurf) - extracted from calf lung lavage fluid
3. Poractant alfa (Curosurf) - extracted from material derived from
minced pig lung

Survanta, surrounded by devices

for its application.

Until recently, Exosurf, Curosurf, Infasurf, and Survanta were the only surfactants FDA approved for use in the
U.S.[9] In 2012 the US FDA approved an additional synthetic surfactant, lucinactant (Surfaxin). Lucinactant
contains the low-complexity 21-amino-acid peptide sinapultide (KL4 acetate), 1,2-dipalmitoyl-sn-glycero-3phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (as the sodium salt), and palmitic acid.
Since Exosurf is no longer marketed in the US, lucinactant is currently the only non-animal-derived surfactant
product available in America.

Surface tension magnitude inside the lung

Even though the surface tension can be greatly reduced by pulmonary surfactant, this effect will depend on the
surfactant's concentration on the interface. The interface concentration has a saturation limit, which depends on
temperature and mixture composition. Because during ventilation there is a variation of the lung surface area,
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the surfactant's interface concentration is not usually at the level of saturation. The surface increases during
inspiration, which consequently opens space for new surfactant molecules to be recruited to the interface.
Meanwhile at the expiration the surface area decreases, the layer of surfactant is squeezed, bringing the
surfactant molecules closer to each other and further decreasing the surface tension.
SP molecules contribute to increase the surfactant interface adsorption kinetics, when the concentration is below
the saturation level. They also make weak bonds with the surfactant molecules at the interface and hold them
longer there when the interface is compressed. Therefore, during ventilation, surface tension is usually lower
than at equilibrium. Therefore the surface tension varies according to the volume of air in the lungs, which
protects them from atelectasis at low volumes and tissue damage at high volume levels.[5][7][8]
Surface tension values
Condition

Tension (mN/m)

Water at 25 C

70

Pulmonary surfactant in equilibrium at 36 C

25

Healthy lung at 100% of TLC

30

Healthy lung between 40 and 60% of TLC

1~6

Healthy lung below 40% of TLC

<1

Production and Degradation

Surfactant production in humans begins in Type II cells during the terminal sac stage of lung development.
Lamellar bodies appear in the cytoplasm 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 100 mg/kg of
surfactant, while preterm infants have an estimated 45 mg/kg at birth.
Club cells also produce a component of lung surfactant.
Alveolar surfactant has a half life of 5 to 10 hours once secreted. It can be both broken down by macrophages
and / or reabsorbed into the lamellar structures of type II pneumocytes. Up to 90% of surfactant DPPC
(dipalmitoyl phosphatidylcholine) is recycled from the alveolar space back into the type II pneumocyte. This
process is believed to occur through SP-A stimulating receptor mediated, clathrin dependent endocytosis.[10]
The other 10% is taken up by alveolar macrophages and digested.

Diseases
Infant respiratory distress syndrome (IRDS) is caused by lack of surfactant, commonly suffered by
premature babies born before 2832 weeks of gestation.
Hyaline membrane disease is an older term for IRDS. It is based on the pathological findings at autopsy
of premature infants. The hyaline membranes were proteinaceous material in the damaged alveoli.
Congenital surfactant deficiency
Pulmonary alveolar proteinosis

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History
In late 1920s von Neergaard[11] identified the function of the pulmonary surfactant in increasing the compliance
of the lungs by reducing surface tension. However the significance of his discovery was not understood by the
scientific and medical community at that time. He also realized the importance of having low surface tension in
lungs of newborn infants. Later, in the middle of the 1950s, Pattle and Clements rediscovered the importance of
surfactant and low surface tension in the lungs. At the end of that decade it was discovered that the lack of
surfactant caused infant respiratory distress syndrome (IRDS).[7]

References
1. "Alveoli and the Breathing Process" (http://www.medicalassistantonlineprograms.org/alveoli/). Retrieved 2013-10-30.
2. West, John B. (1994). Respiratory physiology-- the essentials. Baltimore: Williams & Wilkins. ISBN 0-683-08937-4.
3. Wright, Jo Rae (2004). "Host Defense Functions of Pulmonary Surfactant". Biology of the Neonate 85 (4): 32632.
doi:10.1159/000078172 (https://dx.doi.org/10.1159%2F000078172). PMID 15211087
(https://www.ncbi.nlm.nih.gov/pubmed/15211087).
4. Hills, B. A. (1999). "An alternative view of the role(s) of surfactant and the alveolar model"
(http://jap.physiology.org/cgi/pmidlookup?view=long&pmid=10562593). Journal of applied physiology 87 (5): 1567
83. PMID 10562593 (https://www.ncbi.nlm.nih.gov/pubmed/10562593).
5. Schurch, S.; Lee, Martin; Gehr, Peter; Qanbar, R; Schrch, S (1992). "Pulmonary surfactant: Surface properties and
function of alveolar and airway surfactant". Pure and Applied Chemistry 64 (11): 20920.
doi:10.1351/pac199264111745 (https://dx.doi.org/10.1351%2Fpac199264111745). PMID 11369545
(https://www.ncbi.nlm.nih.gov/pubmed/11369545).
6. Possmayer, Fred; Nag, Kaushik; Rodriguez, Karina; Qanbar, Riad; Schrch, Samuel (2001). "Surface activity in vitro:
Role of surfactant proteins". Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology
129: 209. doi:10.1016/S1095-6433(01)00317-8 (https://dx.doi.org/10.1016%2FS1095-6433%2801%2900317-8).
7. Veldhuizen, Ruud; Nag, Kaushik; Orgeig, Sandra; Possmayer, Fred (1998). "The role of lipids in pulmonary surfactant".
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1408 (23): 90108. doi:10.1016/S09254439(98)00061-1 (https://dx.doi.org/10.1016%2FS0925-4439%2898%2900061-1). PMID 9813256
(https://www.ncbi.nlm.nih.gov/pubmed/9813256).
8. Schrch, Samuel; Bachofen, Hans; Possmayer, Fred (2001). "Surface activity in situ, in vivo, and in the captive bubble
surfactometer". Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 129 (1): 195
207. doi:10.1016/S1095-6433(01)00316-6 (https://dx.doi.org/10.1016%2FS1095-6433%2801%2900316-6).
PMID 11369544 (https://www.ncbi.nlm.nih.gov/pubmed/11369544).
9. Taeusch, H William; Lu, Karen; Ramierez-Schrempp, Daniela (2002). "Improving pulmonary surfactants"
(http://www.chinaphar.com/1671-4083/23/11s.pdf) (PDF). Acta Pharmacologica Sinica. 23 Suppl: 115.
10. Crowther, J. E.; Schlesinger, L. S. (2005). "Endocytic pathway for surfactant protein a in human macrophages: Binding,
clathrin-mediated uptake, and trafficking through the endolysosomal pathway". AJP: Lung Cellular and Molecular
Physiology 290 (2): L33442. doi:10.1152/ajplung.00267.2005 (https://dx.doi.org/10.1152%2Fajplung.00267.2005).
PMID 16169899 (https://www.ncbi.nlm.nih.gov/pubmed/16169899).
11. Neergaard, K. (1929). "Neue Auffassungen ber einen Grundbegriff der Atemmechanik" [New views on a fundamental
concept of respiratory mechanics]. Zeitschrift fr Die Gesamte Experimentelle Medizin (in German) 66 (1): 37394.
doi:10.1007/bf02621963 (https://dx.doi.org/10.1007%2Fbf02621963).

External links
Hane, Francis. "Pulmonary Surfactant Mini-Review" (http://www.readbag.com/leonenkoresearchhttps://en.wikipedia.org/wiki/Pulmonary_surfactant

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uwaterloo-ca-data-lung-surfactant-review).
Retrieved from "https://en.wikipedia.org/w/index.php?title=Pulmonary_surfactant&oldid=662008878"
Categories: Respiratory physiology Integral membrane proteins Surfactants Pulmonary function testing
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