ABSTRACT
I. Introduction 125
II. Evolutionary Origin of Hydrophobic Pulmonary
Surfactant Proteins 126
III. Biological vs. Clinical Engineering of Pulmonary Surfactant 127
IV. Structure-Function Relationships of SP-B 128
V. Structure-Function Relationships of SP-C 132
Acknowledgments 136
References 136
I. Introduction
Decades of research on pulmonary surfactant resulted in a serious paradox that
was not resolved until the mid-1980s. Seminal physiological studies had demon-
strated that lack of surfactant in premature babies was the primary cause of res-
piratory distress syndrome associated with high morbidity and mortality. In
addition, several research groups had shown that administration of an exogenous
surfactant material early after birth of premature animals could prevent and
largely reduce respiratory complications. Suspensions prepared using material
extracted with organic solvents from animal lungs were very efficient as exogen-
ous surfactant. Such organic extractions are routine for separation of the lipid
moiety from biological samples, and hence lipids were soon recognized as
essential components for the biophysical function of surfactant in the lungs.
Extensive physicochemical studies from the early seventies established that the
lipid composition of pulmonary surfactant appeared particularly well suited to
reach and sustain very low surface tensions at low lung volumes during breathing.
The main surface-active molecule in surfactant is a disaturated lecithin, dipal-
mitoylphosphatidylcholine (DPPC), whereas other lipid species are important
to fluidize DPPC enough to facilitate its adsorption at physiological temperature
into the air-liquid interface of lungs. The paradox was that no mixture of purely
synthetic lipids mimicking the composition of natural surfactant worked equally
well in vivo as exogenous surfactant. The key finding that allowed further under-
standing was the discovery of hydrophobic surfactant-associated proteins, now
called SP-B and SP-C. These polypeptides are so hydrophobic that co-isolate
with lipids in organic solvent extractions. On the other hand, they have low anti-
genicity and are not easily identified in routine protein assays. Therefore, until the
1980s, it was unrecognized that these proteins were present in surfactant lipid
extracts.
