Surfactant - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 791

The hydrophobic proteins constitute about 40% of the total protein of lamellar
bodies 10 isolated from pig lungs and about 13% of the total protein of surfactant
isolated from bronchopulmonary lavage fluid [ 1612 ].
Several types of surfactant proteins exist (SPa-SPd) [ 1613 ]. Surfactant proteins
are detected not only in pulmonary acini, but also the digestive, urinary, and
reproductive tracts, as well as synovial and pericardial fluids, various organs, such as
spleen, thymus, and pancreas as well as middle ear and Eustachian tubes. Surfactant
composition depends on tissue type. 11
Hydrophobic surfactant proteins SPb and SPc help release of dipalmitoyl phos-
phatidylcholine. They promote rapid transfer of lamellar bodies from the subphase
to the interface. Proteins SPb and SPc are also involved in protein respreading upon
expansion. They bind preferentially to anionic phospholipids.
Hydrophilic surfactant proteins SPa and SPd that form trimers are members of a
family of collagenous carbohydrate binding proteins, the collectins that are involved
in the immune system. Collectins are a subset of calcium-dependent C-type lectins
that bind carbohydrates. Both SPa and SPd interact with viruses, bacteria, fungi,
and allergens. They are thus present in extrapulmonary tissues. Proteins SPa and
SPd bind to alveolar macrophages.
Hexadecameric SPa is the most abundant surfactant protein. Protein SPa is
the product of 2 distinct genes on chromosome 10q22-q23: SPa1 and SPa2. It is
involved in the structural organization of surfactant. 12 Protein SPa that is necessary
for tubular myelin production is implicated in spacing of common and tubular
myelins.
Functions of SPa include surface tension lowering in combination with phos-
pholipids in the form of tubular myelin, maintenance of surfactant protein pool
homeostasis, and defense against pathogens. Protein SPa increases phagocytosis
of cells infected by Streptococcus pneumoniae, Haemophilus influenza, respiratory
syncytial virus (Pneumovirus), and herpes virus (Simplexvirus), among other
pathogens [ 1559 ]. It also modulates uptake and secretion of phospholipids by iso-
lated type-2 alveolar cells in vitro, hence balancing surfactant release and clearance.
Moreover, SPa improves adsorption of compounds made of phospholipids and
hydrophobic proteins.
Dimeric SPb is encoded by the spb gene that belongs to chromosome 2. Protein
SPb is a member of a family of saposins that are sphingolipid activators. 13

It

10 Lamellar bodies are granules that contain SPa to SPc and lipids [ 1611 ].
11 The ratio of phosphatidylcholine to sphyngomyelin varies from 2:1 in Eustachian tube surfactant
to 67:1 in lung surfactant [ 1559 ]. In particular, dipalmitoyl phosphatidylcholine concentration is
much higher in lung surfactant than in that of Eustachian tube surfactant.
12 Protein SPa neck domain is involved in protein trimerization. Its globular C-terminus acts in lipid
binding as well as formation and stabilization of curved membranes. Protein SPa exists in open or
closed forms according to the medium composition. Calcium ions produce the closed structure
of 6 trimers. The N-terminus of SPa protein is required for oligomerization as well as binding
and aggregation of phospholipids [ 1614 ]. Its collagen-like domain is involved in SPa stability and
oligomerization. It contributes to SPa shape and dimension.
13 Saposins activate several lysosomal hydrolases involved in sphingolipid metabolism.