Production and components of surfactant
Surfactant is a product of the alveolar type 2 cells. This complex
mixture of lipids and proteins starts being secreted into the alveoli
form 24 weeks gestational age[13]. Following synthesis in the
endoplasmic reticulum and Golgi apparatus, [14]surfactant is
packaged in lamellar bodies[15] before exocytosis. The
Adenosine Triphosphate Binding
Cassette 3 (ABCA3) protein that is located on the limiting membrane of
the lamellar body facilitates transport of phospholipids into the
lamellar bodies[16]. After exocytosis into the alveolar surface,
hydrophobic proteins become essential in the formation of the lipid
monolayer at the air-liquid interface. This mixture forms a film that is
made up of a lipid bilayer and a monolayer enriched with
dipalmitoylphosphatidylcholine that is mostly responsible to lower
surface tension in the air fluid interface of the alveoli[17].
Surfactant is made up of 90% phospholipids and 10% protein. The major
component of phospholipid is phospatidylcholine which in about 80%
exists in the dipalmitoylphosphatidylcholine form[18]. The next
component of phospholipids is phospatidylglycerol that may play a
secondary role in reducing surface tension. It has been demonstratedin vitro that mixtures with dipalmitoylphosphatidylcholine:
phospatidylglycerol has better lipid adsorption when compared to
mixtures with dipalmitoylphosphatidylcholine alone[19, 20].
Additionally, studies have demonstrated that phospatidylglycerol plays a
part in the innate immune pathway and regulates both viral and bacterial
infections[21-23]. The remainder of phospholipid components are made
up of phosphatidylethanolamine, phosphatidylinositol,
phosphatidylserine, sphingomyelin and neutral lipids (cholesterol and
diacylglycerol), the exact function of these components remains
unclear[24].
The protein component of
surfactant is comprised of 4 protein types namely surfactant protein A
(SP-A), Surfactant protein B (SP-B), Surfactant protein C (SP-C) and
surfactant protein D (SP-D)[25]. These proteins can be divided into
two groups based on their chemical properties, SP-B and SP-C are two
small hydrophobic proteins, while SP-A and SP-D are
hydrophilic. In addition toABCA3 , Thyroid transcription factor-1 (TTF-1) is also an
important protein required for the normal structure and functioning of
pulmonary surfactant [26].
SP-A was the first protein to be discovered as a component of
surfactant[27]. SP-A and SP-D function as part of the innate immune
system[11, 28] as opsonins that act against pathogens by increasing
membrane permeability or facilitating the attachment of
phagocytes[29]. SP-A deficient animal models are more susceptible to
infections but at the same time able to maintain normal oxygenation,
suggesting that SP-A does not influence the normal functioning of
surfactant[23].
SP-B and SP-C are of particular
interest in congenital surfactant protein deficiencies. SP-B and SP-C
molecules are first synthesised as larger precursor molecules that are
further cleaved into their mature forms. This process occurs in the
lamellar body and it is here that ABCA3 enables phospholipid
translocation and organelle development. ABCA3 (ATP-binding cassette,
subfamily A, member 3) is an intracellular lipid transporter that is
localized within the outer membrane of lamellar bodies in which
transports phospholipids and cholesterol into the lamellar body
lumen[30]. Lamellar bodies function as a production and storage
organelle for surfactant before secretion into the alveolar
space[31].
The production of these molecules is under the control of TTF1 or NKX2.1
which is a nuclear transcription factor that also is expressed in the
basal ganglia and thyroid gland[32, 33].