Pulmonary Surfactant: The Key to the Evolution of
Air Breathing
Christopher B. Daniels and Sandra Orgeig
Department of Environmental Biology, University of Adelaide, Adelaide, South Australia 5005, Australia
Pulmonary surfactant controls the surface tension at the air-liquid interface within the lung. This system had a single evolutionary origin that predates the evolution of the vertebrates and lungs. The
lipid composition of surfactant has been subjected to evolutionary selection pressures, particularly temperature, throughout the evolution of the vertebrates.
ungs have evolved independently on several occasions
over the past 300 million years in association with the radiation and diversification of the vertebrates, such that all major
vertebrate groups have members with lungs. However, lungs
differ considerably in structure, embryological origin, and
function between vertebrate groups. The bronchoalveolar lung
of mammals is a branching “tree” of tubes leading to millions
of tiny respiratory exchange units, termed alveoli. In humans
there are ~25 branches and 300 million alveoli. This structure
allows for the generation of an enormous respiratory surface
area (up to 70 m2 in adult humans). Generally, in nonmammals, lungs are baglike with either smooth walls or large, bellows-shaped respiratory units (termed faveoli) extending from
the outer wall of the lung into a central air space. Birds have
the most strikingly different lung structure, with a pair of small
parabronchial lungs connected to a series of air sacs. Air is
propelled via the airsacs, which act like bellows, in a unidirectional manner through the lung. The lungs consist of a
series of tubes (parabronchi) from which emanate the verysmall-diameter, rigid air capillaries, which lie in close apposition with blood capillaries and represent the site of gas
exchange. Some reptiles and amphibians have a complex and
dense arrangement of septate compartments. However, in
contrast to mammals, the lungs of fish, amphibians, and reptiles always lack a bronchial tree, a diaphragm, and a separate
pleuroperitoneal chamber, and they have respiratory units up
to 100 times larger than alveoli of similar-sized mammals.
But all lungs have one common characteristic. They are
internal, fluid-lined, gas-holding structures that inflate and
deflate cyclically. As a result, all lungs face potential problems
related to the surface tension of the fluid. Pulmonary surfactant is produced in the lung to decrease surface tension of this
fluid lining (hypophase). Von Neergaard (quoted in Ref. 6) first
demonstrated that the surface forces at the gas-liquid interface
of the lung contribute substantially to the retractive pressure,
and hence static compliance, of the lung. However, surfactant
can also vary surface tension with the radius of curvature of
each alveolus (or more accurately, regions within an alveolus)
so that the pressures within all alveoli are maintained at similar values, permitting alveoli of different sizes to coexist. Surfactant also helps the narrowest airways to remain open,
thereby reducing the resistance to air flow and controlling
fluid balance in the lung. However, the alveoli, being interde0886-1714/03 5.00 © 2003 Int. Union Physiol. Sci./Am. Physiol. Soc.
www.nips.org
Downloaded from http://physiologyonline.physiology.org/ by 10.220.32.246 on June 16, 2017
L
pendent units, do not necessarily stretch upon inflation but
unpleat or unfold in a complex manner. Moreover, the many
fluid-filled corners and crevices in the alveoli open and close
as the lung inflates and deflates.
Surfactant in nonmammals exhibits an antiadhesive function, lining the interface between apposed epithelial surfaces
within regions of a collapsed lung. As the two apposing surfaces peel apart, the lipids rise to the surface of the hypophase
fluid at the expanding gas-liquid interface and lower the surface tension of this fluid, thereby decreasing the work required
to separate the two surfaces. However, for surfactant to act as
an antiadhesive, the respiratory tissues must “fold” in on themselves, possibly during exhalation, or when the ventilatory
period is punctuated by protracted nonventilatory periods at
low lung volume. These conditions occur frequently in the
ventilatory pattern of nonmammals.
The pulmonary surfactant system
Pulmonary surfactant is a complex mixture of phospholipids (PL), neutral lipids [particularly cholesterol (Chol)], and
proteins. The PL are assembled in the endoplasmic reticulum
and the Golgi apparatus of alveolar type II cells and are stored
in lamellar bodies until exocytosis (Fig. 1). The assembly of the
surfactant proteins into lamellar bodies is less clear and may
proceed via the endoplasmic reticulum and Golgi apparatus
to multivesicular bodies before combining with the lamellar
bodies (10). The source(s) of alveolar Chol remains unknown
(16). The lamellar bodies consist of a dense proteinaceous
core with lipid bilayers arranged in concentric, stacked lamellae surrounded by a limiting membrane. After the lamellar
bodies have been released into the alveolar space, they swell
and unravel into a characteristic cross-hatched structure
termed tubular myelin (Fig. 1). It is this structure that supplies
the lipids for the surface film, which regulates the surface tension of the liquid lining the lung (10).
The ability to lower and vary surface tension with changing
surface area is attributed to the interactions between the disaturated PLs (DSPs), particularly dipalmitoylphosphatidylcholine (DPPC), and the other lipids, such as the unsaturated
PLs (USPs) and Chol. Upon expiration, dynamic compression
of the mixed surfactant film results in the “squeezing out” of
USP and Chol, such that the surface film is enriched in DPPC
News Physiol Sci 18: 151157, 2003;
10.1152/nips.01438.2003
151
Downloaded from http://physiologyonline.physiology.org/ by 10.220.32.246 on June 16, 2017
FIGURE 1. A: schematic diagram of the life cycle of pulmonary surfactant (moving from bottom to top). Pulmonary surfactant components are synthesized in
the endoplasmic reticulum (ER), transported to the Golgi aparatus, and packaged into lamellar bodies (LB). LB are secreted into the liquid lining the alveoli
(hypophase) via exocytosis across the type II cell plasma membrane. Here the lamellar bodies swell and unravel, forming a cross-hatched structure termed tubular myelin (TM), which consists of lipids and proteins. This structure supplies lipids to the surface film as well as the surface-associated phase (SAP). As the mixed
molecular film is compressed, lipids are squeezed out of the film into the SAP to produce a dipalmitoylphosphatidylcholine (DPPC)-enriched film that is capable of reducing surface tension (ST) to near 0 mN/m. It is possible that some lipids from the SAP reenter the surface film (dashed arrow). Lipids from the surface
film and the SAP are eventually recycled and taken back up by the type II cell via endocytosis. The role of some of the surfactant proteins (SP-A, -B, and -C) in
regulating these processes is indicated with n (stimulation) or p (inhibition). Reproduced with permission from Elsevier from Ref. 17. B: structure of the lung
epithelium of the lizard Ctenophorus nuchalis, demonstrating the location of type II cells (t) in between the capillaries (c), which bulge into the airspace. The
capillaries contain macrophages (m) and erythrocytes (r). Surfactant material (s) has been extruded into the airspace. C: electron micrograph demonstrating the
surfactant structures: lamellar bodies (lb) and tubular myelin (tm) in the airspace of a lizard lung. B and C are reprinted with permission from Ref. 14.
(Fig. 1A). The DPPC molecules can be compressed tightly
together by virtue of their two fully saturated fatty acid chains.
In so doing, they exclude water molecules from the air-liquid
interface, thereby eliminating surface tension (19).
Lipids can exist in either a fluid liquid-crystalline state or in
a solid gel state. The transition between these two phases
occurs at the phase transition temperature (Tm) of that lipid.
For the surfactant lipids to spread over the alveolar surface
upon inspiration, the surfactant film must exist in the liquidcrystalline state. Because DPPC has a Tm of 41°C, a pure
DPPC film will exist in the gel form at mammalian body temperatures and hence adsorb extremely slowly to the air-liquid
interface (19). The addition of other lipids, e.g., Chol or USP,
152
News Physiol Sci • Vol. 18 • August 2003 • www.nips.org
into the surface film upon inspiration lowers the Tm of the lipid
mixture, enabling it to exist in the fluid state at the same body
temperature. In this state, the lipids are able to disperse to coat
the surface of the expanding fluid layer.
Temperature therefore has a profound influence on the
structure and function of surfactant lipids. Given that the
majority of animals have much lower body temperatures than
homeothermic mammals, how can animals regulate the fluidity of their surfactant film at low and/or fluctuating body temperatures? Furthermore, the low metabolic rates of nonmammals also have profound implications for the rates of synthesis
of new components. Hence, for example, the need for additional quantities of USP in surfactant requires PL synthesis,
the surfactant-secreting cells migrated with the air-filled outpouchings of the gut before the lung surfactant took on its current surface tension-controlling functions. Hence the surfactant system predated the evolution of lungs and was crucial for
the evolution of air breathing.
Surfactant and the evolution of air breathing
Here we examine the evolution of the surfactant system in
association with three of the major evolutionary steps for the
vertebrates: 1) the separation of the Actinopterygiian (bony)
fish from the Sarcopterygiia (lungfish) and the Tetrapods (landdwelling vertebrates); 2) the “Land-Water Transition”; and 3)
changes in body temperature, particularly the general pattern
of increasing from cold ectotherms to warm heliotherms and
endotherms. An evolutionary analysis of surfactant composition of the vertebrates ranging from air-breathing fish, teleosts,
and lungfish to amphibians, reptiles, birds, and mammals has
revealed that fish lungs and the lungs of the primitive Australian lungfish, Neoceratodus forsteri, have surfactant with
approximately threefold greater amounts of Chol relative to PL
than any of the other vertebrate groups (5, 15) (Fig. 2B). However, DSP as a percentage of PL demonstrates the opposite
trend, with only the mammals and some reptiles having high
levels of 4050% (5, 6) (Fig. 2C). Teleost swimbladders and
the lungs of the air-breathing fish and N. forsteri contain PLs
that are two- to fourfold less saturated than those of the
derived dipnoans, the African and South American lungfish,
and the majority of the amphibians and fivefold less than
those of reptiles and mammals (5, 6). These opposite trends in
Chol/PL and DSP/PL ratios result in a very dramatic pattern for
the Chol/DSP ratio (5, 16). The fish and N. forsteri with their
relatively simple baglike lungs have a Chol/DSP ratio up to an
order of magnitude greater than the reptiles and mammals.
The amphibians and the derived Dipnoans have intermediate
levels of Chol relative to DSP, i.e., the ratio is approximately
double that of the reptiles and mammals (6, 16).
Differences among terrestrial groups in the composition of
surfactant probably reflect the temperature-dependent fluidity
of surfactant PL. Because DPPC undergoes a phase transition
“...surfactant had a single evolutionary origin
that predated the evolution
Downloaded from http://physiologyonline.physiology.org/ by 10.220.32.246 on June 16, 2017
which may take some time. Hence USPs do not appear to be
appropriate for controlling fluidity of surfactant in the face of
the very rapid or step changes in body temperature, which
commonly occur in most nonmammals and in torpid or hibernating mammals.
Chol is able to affect the fluidity of PLs directly. Chol is
thought to increase the separation between PL molecules, thus
disrupting the intermolecular interactions between their head
groups and allowing greater rotational movement. At 10% by
weight, or 20 mol%, Chol is the second most abundant lipid
component of pulmonary surfactant. Although the source of
surfactant Chol is not known, the ready availability of Chol in
the alveolar compartment and in the circulating plasma makes
this molecule a good candidate for the rapid regulation of surfactant fluidity (16). Hence, titrating the Chol/DSP ratio in the
face of rapid body temperature changes is an excellent
method for maintaining fluidity and a functional surfactant at
low body temperatures.
The protein component of pulmonary surfactant represents
~10% by weight, and four surfactant proteins have been
described. These are SP-A, SP-B, SP-C, and SP-D, which are
synthesized in alveolar type II cells and are all associated with
purified surfactant (11). Both the secretion and the reuptake of
surfactant PLs into type II cells appear to be regulated by SPA. Both SP-A and SP-B are essential for the formation and
structural integrity of surfactant components (Fig. 1A). The
hydrophobic surfactant proteins, SP-B and SP-C, strongly
interact with the lipids and promote the formation and adsorption of the surface film to the air-liquid interface. However, the
hydrophilic surfactant proteins, SP-A and SP-D, are predominantly involved in the innate host-defense system of the lung
(11).
Using surfactant protein analysis, we determined that surfactant had a single evolutionary origin that predated the evolution of the vertebrates. We demonstrated that an SP-A-like
protein is present in surfactant from all vertebrate classes,
including in goldfish swimbladders (20) (Fig. 2A). Furthermore, the ultrastructure of the surfactant system is highly conserved. Lamellar bodies and tubular myelin-like structures
have been observed in the lungs of reptiles (Fig. 1), birds, and
amphibians. Lamellar bodies have been observed in the three
extant species of lungfish, in the lungs of primitive air-breathing fish, and in the swimbladder of the rainbow trout. Thus
surfactant from nonmammalian vertebrates appears to be produced, stored, and released in a similar manner to mammalian surfactant. Moreover, the system predates the evolution of lungs (reviewed in Ref. 4).
Lungs developed as out-pouchings of the gut, and the primary selection pressure for the evolution of lungs was probably aquatic hypoxia (18). The ancestral bony vertebrate was
most likely lunged, inhabiting warm stagnant pools and gulping air to gain sufficient oxygen. The cells that produce surfactant, and contain SP-A, have been located in the gut of
mammals (9). In the gut, surfactant may be important in controlling fluid-fluid interactions between liquids of different viscosities (e.g., the mucus and serous fluid layers). Alternatively,
or perhaps additionally, gut surfactant may be involved in
innate immunity (11). Hence it makes sense to propose that
of the vertebrates.”
from a gel to a liquid-crystalline state at 41°C, and realistically
only homeotherms and the most heliothermic of the reptiles
are likely to have body temperatures that approach this value,
it follows that only these groups are likely to be capable of tolerating high DSP/PL ratios (5) (Fig. 2C). In contrast, advanced
Dipnoans and amphibians generally have much lower body
temperatures and have incorporated less DSP in their surfactant, with DSP/PL ratios of only 1530% (5). Chol is not as
effective as DSP at reducing surface tension but is able to
lower the normal Tm of DSP, thereby maintaining the mixture
News Physiol Sci • Vol. 18 • August 2003 • www.nips.org
153
in a fluid, easily adsorbable state over a much broader range
of temperatures (reviewed in Ref. 16). Similarly, USP have a
much lower Tm than their saturated counterparts. The surfactant of fish and amphibians, having greater Chol/DSP ratios
(20130%) compared with those of the warmer reptiles and
mammals (1015%), appear to benefit from this increased fluidity (5, 6). Bats have the lowest amount of surfactant Chol
ever recorded. The two species we examined had 6 and 15
times less surfactant Chol than all other mammals studied to
date (1) (Fig. 2B). The extraordinarily complex structure of bat
lungs, with the tiny alveoli and high ventilatory capacity, correlates with the most sophisticated surfactant so far recorded.
It also appears that the combination of extremely high surfactant Chol and very low DSP may be a universal function of
154
News Physiol Sci • Vol. 18 • August 2003 • www.nips.org
Downloaded from http://physiologyonline.physiology.org/ by 10.220.32.246 on June 16, 2017
FIGURE 2. A: Western blot analysis of lavage protein
probed with a rabbit anti-human SP-A polyclonal antibody. The antibody cross-reacted with all species
examined, with predominant cross-reactivity at
molecular weights of 5565 kDa (dimer) and less at
2835 kDa (monomer) and 120 kDa (tetramer).
Species are: mouse (Mus musculus), dunnart
(Sminthopsis crassicaudata), crocodile (Crocodylus
porosus), sea turtle (Caretta caretta), freshwater turtle
(Emydura kreffti), salamander (Amphiuma tridactylum), African lungfish (Protopterus annectens), Australian lungfish (Neoceratodus forsteri), bichir
(Polypterus senegalensis), gar (Lepisosteus osseus), and
goldfish (Carassius auratus). Reprinted with permission from Ref. 20. B and C: Cholesterol/phospholipid
ratio (Chol/PL; Pg/Pg; B) and disaturated phospholipid/phospholipid ratio (% DSP/PL; C) expressed as a
percentage of total phospholipid of lavage material
obtained for a range of air-breathing vertebrates.
Species are: teleost fish, the goldfish C. auratus (C.aur)
(5); the air-breathing Actinopterygiian fishes P. senegalensis (P.sen), Calamoicthys calabaricus (C.cal), and
L. osseus (L.oss) (5); the Australian and African lungfish
N. forsteri (N.for) and P. annectens (P.ann) (15); the
tiger salamander Ambystoma tigrinum (A.tig) (5); the
amphibians A. tridactylum (A.tri), Siren intermedia
(S.int), Bufo marinus (B.mar), and Xenopus laevis
(X.lae) (5); the rattlesnake Crotalus atrox (C.atr) (8); the
lizard Ctenophorus nuchalis (C.nuc) (2); the chicken
Gallus gallus (G.gal) (12); the rat Rattus norvegicus
(R.nor) (5); human (H.sap) (5); the fat-tailed dunnart
Sminthopsis crassicaudata (S.crass) (13); and the
microchiropteran bats Nyctophilus geoffroyi (N.geoff)
and Chalinolobus gouldii (C.goul) (1). The lizard, the
dunnart, and the bats were at their warm-active body
temperature (3337°C). Data are expressed as means
± SE; n = 49.
simple, largely avascular lungs, which are either not used or
only infrequently used for respiratory purposes (16). This is
supported by the fact that the smooth baglike or saccular lung
used for gas storage in the rattlesnake has a threefold greater
Chol/DSP ratio than the septated faveolar lung containing the
respiratory tissue (8). Furthermore, the goldfish swimbladder,
which is an internal gas-holding structure that is used predominantly for buoyancy, had one of the highest Chol/DSP
ratios of any surfactant system (5). It is not clear why lungs and
swimbladders have such high relative proportions of Chol. Is
it a primitive feature, or does it represent an adaptive requirement? Possibly it is related to an increased need for spreadability in organs where the surfactant secretory cells are relatively few and far between. Alternatively, Chol may represent
fluidity (2). Similar changes in surfactant Chol occur in
response to torpor in the fat-tailed dunnart, Sminthopsis crassicaudata, a desert-dwelling marsupial capable of reducing its
body temperature to as little as 13°C for an average of 8 h and
a maximum of 19 h. The absolute amounts of Chol and PL
increased by up to 50% after as little as 1 h of torpor, and the
Chol/PL and Chol/DSP ratios increased after 8 h in torpor (13).
Similarly, an increase in Chol relative to total PL and DSP
occurred in the microchiropteran bat, Chalinolobus gouldii, in
response to a torpor bout at a body temperature of 25°C.
However, another microchiropteran bat, Nyctophilus geoffroyi, which has the lowest Chol level ever recorded in a mammal, did not demonstrate this classic pattern (1).
Downloaded from http://physiologyonline.physiology.org/ by 10.220.32.246 on June 16, 2017
a primitive antioxidant, protecting the inner lining from oxidative damage. However, because fish surfactant is so simple,
poorly surface active, dominated by Chol, and located within
lungs only occasionally used for respiration (i.e., these species
are facultative air breathers), we have termed the surfactant of
fish and the Australian lungfish the “protosurfactant” (16).
In addition to the large-scale evolutionary changes attributable to temperature as the primary selection pressure, temperature is also the major acute controller for the lipid composition of surfactant. The first documentation that alveolar surfactant Chol can change dynamically in response to a physiological change occurred in the lizard, Ctenophorus nuchalis (2).
This central Australian lizard withstands variations in body
temperature from 13 to 44°C, with a mean preferred temperature of 36.4°C (2). A step decrease in temperature from 37 to
19 or 14°C for 4 h increased the Chol/PL ratio from 8% at
37°C to 15% at 19°C and 18% at 14°C (2). The increase in the
ratio was due solely to an increase in the amount of Chol.
Changes in the ratio were evident after as little as 2 h and were
maintained for up to 48 h. Hence it appears that at low body
temperatures the animals respond by selectively increasing
the level of Chol in their surfactant, presumably to maintain
What is the evolutionary significance in surfactant
function?
We have proposed that the main function of surfactant in
nonmammals is to act as an antiadhesive that prevents adhesion of adjacent epithelial surfaces at low lung volumes (5)
(Fig. 3, A and B). If the fluid lining the tissue-tissue interface
has a high surface tension, then the work of initially separat-
FIGURE 3. Scanning electron micrograph of the
faveoli of the lizard C. nuchalis during the breathing
cycle. A: lung is inflated and the faveolar walls are
not closely opposed. B: lung is deflated and opposing sheets of epithelial tissue are in close contact,
particularly in the corners. o, Outer wall of lung; t,
trabecular network; e, epithelial surface of faveoli.
Reprinted with permission from Ref. 3. C: transmission electron micrograph showing surfactant material preventing the adherence of adjacent epithelial
surfaces in the lung of C. nuchalis. Reprinted with
permission from Ref. 14. D: mechanism of airflow
(thick arrows) into and out of the faveoli (f) during
breathing in the lizard. At expiration (thin arrows) the
ribs move the outer wall (o) of the lung toward the
trabecular network (t), folding the faveoli like a bellows, decreasing volume and pushing air into the
central air space. Upon inspiration, the outward
movement of the ribs pulls the outer wall of the lung
away from the inner trabecular network, increasing
the volume of the faveoli. Air enters the faveoli from
the central air space as the faveolar volume
increases. Note that the trabeculae and the “mouth”
of the faveoli do not change shape or location during
breathing. Reprinted with permission from Elsevier
from Ref. 4.
News Physiol Sci • Vol. 18 • August 2003 • www.nips.org
155
tion of irritants, and also prevent the lung from collapsing or
filling with fluid. There are some constants in the evolution of
aerial breathing, particularly the presence of a surfactant system. It appears that a surfactant system evolved before the
evolution of lungs in vertebrates. It also appears that there are
two different types of surfactant: one in the Actinopterygiian
fishes, which is high in Chol and USP, and one in the Sarcopterygiian fishes and tetrapods, which is relatively low in
Chol and USP and higher in DSP. The fish surfactant is highly
spreadable but not very surface active. The tetrapod surfactant
is much more surface active and may have enabled the development of more complex lungs with smaller respiratory units
and a greater total respiratory surface area, paving the way for
the occupation of land. It is possible that fish surfactant is a
“protosurfactant” that evolved into tetrapod surfactants but
was retained as a protective lipid lining for the gas bladders in
the modern fish and in gas-holding structures that are not used
for respiration.
Within the tetrapods, the concentration of DSP increases
with the evolution from cold, wet ectotherms (amphibians) to
Downloaded from http://physiologyonline.physiology.org/ by 10.220.32.246 on June 16, 2017
ing the tissues will be high. As the surfaces are further separated and the fluid retreats to the corners, surface tension
should play a smaller and smaller role in the work of breathing. Without an agent to lower the surface tension of the fluid
intervening between the contacting epithelial surfaces (Fig.
3C), inspiration after lung collapse might be impossible, or at
least extremely costly. The antiadhesive property of surfactant
is therefore a biological manifestation of the ability of the
lipids to lower surface tension.
Using scanning electron microscopy and computerized
tomography scanning, a model was developed for the breathing dynamics of the lizard, Ctenophorus nuchalis (3). During
lung deflation, the epithelial tissues, which are strung between
the outer lung wall and the inner trabecular network, fold in
on each other like a concertina (Fig. 3D). This causes large
portions of epithelial tissue to come into contact, a situation in
which the antiadhesive function of surfactant may be critical.
Such a function can be demonstrated in nonmammalian vertebrates (reptiles, Actinopterygiian fish, and salamanders) by
demonstrating an increase in opening pressure following the
removal of surfactant by rinsing with isotonic saline, a process
termed lavage (5). Opening pressure is defined as the pressure
required to inflate a completely collapsed isolated lung (Fig. 4,
A and B). Surfactant also performed an antiadhesive function
in the goldfish swimbladder (7). Furthermore, in almost all
cases, filling pressure (i.e., the pressure required to continue to
inflate the lung after initial lung opening) was extremely low
(14 cmH2O) and remained unchanged before and after
lavage (5). Therefore, the surfactant lipids appear to be important only during the initial phase of inflating a collapsed lung
and not during further inflation.
The pattern and mode of breathing of nonmammalian vertebrates also indicate that an antiadhesive function might be
essential for these animals, particularly when they are very
cold. The aquatic amphibians Amphiuma and Siren collapse
their lungs completely upon expiration, as do dipnoan lungfish and Polypterus. Complete collapse of the lung may also
occur at end-expiration in some small frogs, and sea snakes
cycle air by emptying and collapsing the saccular lung
(reviewed in Ref. 5). Furthermore, at low body temperatures,
the lizard C. nuchalis exhibits periods of apnea during which
the lungs collapse and the epithelial surfaces may come into
contact (5). The low metabolic rate of cold ectotherms
decreases the need for frequent ventilations, and the lungs
collapse for prolonged periods. Here surfactant is critical to
decrease the work of separating the contacting epithelial surfaces when the occasional breath is required.
Conclusion
One of the great steps in vertebrate evolution has been the
development of an internal lung. However, despite the morphological diversity of lungs, they are all essentially internal,
fluid-lined structures that cycle air by changing volume. Moreover, lungs all face similar physical challenges. Organisms
must maximize the surface for gas exchange while maximizing lung compliance to minimize the work of breathing. They
must minimize the threat of infection, prevent the accumula156
News Physiol Sci • Vol. 18 • August 2003 • www.nips.org
FIGURE 4. Opening pressure of the lungs of nonmammalian vertebrates. A:
schematic representation of the pressure required to open and then fill a completely collapsed lung with air infused at a constant rate (usually 1 ml/min).
Note that initially the pressure increases before the lung begins to inflate, then
once open the lung inflates with little change in pressure. B: the opening pressure before and after surfactant removal by lavage of collapsed lungs from a
range of vertebrates. T.ord, Thamnophis ordinoides (garter snake). Other
abbreviations are as for Fig. 2. Data are expressed as means ± SE; n = 48.
Reprinted with permission from Ref. 6.
This work was funded by the Australian Research Council.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
References
1. Codd JR, Daniels CB, and Orgeig S. Thermal cycling of the pulmonary
surfactant system in small heterothermic mammals. In: Life in the Cold.
Eleventh International Hibernation Symposium, edited by Heldmeier G
and Klingenspor M. Berlin: Springer-Verlag, 2000, p. 187197.
2. Daniels CB, Barr HA, Power JHT, and Nicholas TE. Body temperature
alters the lipid composition of pulmonary surfactant in the lizard
Ctenophorus nuchalis. Exp Lung Res 16: 435449, 1990.
3. Daniels CB, McGregor LK, and Nicholas TE. The dragon’s breath: a model
for the dynamics of breathing and faveolar ventilation in agamid lizards.
Herpetologica 50: 251261, 1994.
4. Daniels CB and Orgeig S. The comparative biology of pulmonary surfactant: past, present and future. Comp Biochem Physiol A 129: 936, 2001.
5. Daniels CB, Orgeig S, and Smits AW. Invited Perspective: The evolution of
17.
18.
19.
20.
the vertebrate pulmonary surfactant system. Physiol Zool 68: 539566,
1995.
Daniels CB, Orgeig S, Wood PG, Sullivan LC, Lopatko OV, and Smits AW.
The changing state of surfactant lipids: new insights from ancient animals.
Am Zool 38: 305320, 1998.
Daniels CB and Skinner CH. The composition and function of surface
active lipids in the goldfish swim bladder. Physiol Zool 67: 12301256,
1994.
Daniels CB, Smits AW, and Orgeig S. Pulmonary surfactant lipids in the
faveolar and saccular lung regions of snakes. Physiol Zool 68: 812830,
1995.
Engle MJ and Alpers DH. Surfactant-like particles mediate tissue-specific
functions in epithelial cells. Comp Biochem Physiol A 129: 163171,
2001.
Goerke J. Pulmonary surfactant: functions and molecular composition.
Biochim Biophys Acta 1408: 7989, 1998.
Haagsman HP and Diemel RV. Surfactant-associated proteins: functions
and structural variation. Comp Biochem Physiol A 129: 91108, 2001.
Johnston SD, Orgeig S, Lopatko OV, and Daniels CB. Development of the
pulmonary surfactant system in two oviparous vertebrates. Am J Physiol
Regul Integr Comp Physiol 278: R486R493, 2000.
Langman C, Orgeig S, and Daniels CB. Alterations in composition and
function of surfactant associated with torpor in Sminthopsis crassicaudata. Am J Physiol Regul Integr Comp Physiol 271: R437R445, 1996.
McGregor LK, Daniels CB, and Nicholas TE. Lung ultrastructure and the
surfactant-like system of the central netted dragon, Ctenophorus nuchalis.
Copeia 1993: 326333, 1993.
Orgeig S and Daniels CB. The evolutionary significance of pulmonary surfactant in lungfish (Dipnoi). Am J Respir Cell Mol Biol 13: 161166, 1995.
Orgeig S and Daniels CB. The roles of cholesterol in pulmonary surfactant: insights from comparative and evolutionary studies. Comp Biochem
Physiol A 129: 7589, 2001.
Orgeig S, Daniels CB, and Sullivan LC. The development of the pulmonary surfactant system. In: The Lung: Development, Aging and the
Environment, edited by Harding R, Pinkerton K, and Plopper C. London:
Academic, 2003.
Perry SF. Structure and function of the reptilian respiratory system. In:
Comparative Pulmonary Physiology. Current Concepts (1st ed.), edited by
Wood SC. New York: Marcel Dekker, 1989, p. 193236.
Possmayer F. Physicochemical aspects of pulmonary surfactant. In: Fetal
and Neonatal Physiology, edited by Polin RA and Fox WW. Philadelphia:
W. B. Saunders, 1997, p. 12591275.
Sullivan LC, Daniels CB, Phillips ID, Orgeig S, and Whitsett JA. Conservation of surfactant protein A: evidence for a single origin for vertebrate
pulmonary surfactant. J Mol Evol 46: 131138, 1998.
Downloaded from http://physiologyonline.physiology.org/ by 10.220.32.246 on June 16, 2017
warm heliotherms and endotherms (some reptiles, birds, and
mammals). It appears that the DSP/PL ratio is set by the “thermal programming” of the animal and does not represent a
short-term method for maintaining fluidity. Chol declines in
importance with the evolution of the vertebrates but retains an
important function as a “rapid-response” method of maintaining fluidity of the surfactant lipids, particularly for ectotherms
or heterothermic mammals faced with major diurnal fluctuations in body temperature.
The majority of nonmammalian lungs are essentially
baglike, without a bronchial tree, and with only a few exceptions (e.g., tracheal lungs of snakes or parabronchial lungs of
birds) regularly collapse completely. An important function of
surfactant in these lung types is to prevent the epithelial surfaces from adhering to each other. But nonmammalian surfactant does not influence inflation compliance. Because there is
little doubt that lungs of this type, and breathing patterns of
this nature, represent the primitive form, we hypothesize that
acting as an antiadhesive may be the original function of surfactant, but one which led naturally to the alveolar stability
and compliance roles that dominate mammalian surfactant
function.
News Physiol Sci • Vol. 18 • August 2003 • www.nips.org
157