Pulmonary Surfactant Pathophysiology: Current Models and Open Questions
Jesús Perez-Gil and Timothy E. Weaver



Abstract

Pulmonary surfactant is an essential lipid-protein complex that stabilizes the respiratory units (alveoli) involved in gas exchange. Quantitative or qualitative derangements in surfactant are associated with severe respiratory pathologies. The integrated regulation of surfactant synthesis, secretion, and metabolism is critical for air breathing and, ultimately, survival. The goal of this review is to summarize our current understanding and highlight important knowledge gaps in surfactant homeostatic mechanisms.

The vital process of mammalian breathing is dependent on an extensive gas exchange surface provided by the alveoli in the lung periphery. Surface tension on the epithelial side of the air-blood barrier exerts a collapsing pressure that is stabilized by spreading of a lipid-rich film (pulmonary surfactant) at the alveolar air-liquid interface. Quantitative [e.g., respiratory distress syndrome (RDS)] or qualitative [e.g., acute RDS (ARDS)] changes in surfactant lead to alveolar collapse and the need for ventilatory support; likewise, accumulation of surfactant in the alveolar airspaces (e.g., pulmonary alveolar proteinosis) impedes gas exchange. Thus the integrated regulation of surfactant synthesis, secretion, and metabolism is essential for air breathing and, ultimately, survival.

Research in the past three decades has provided extensive insight into surfactant biology that, in turn, has facilitated development of surfactant replacement therapies: the latter have profoundly impacted the incidence of morbidity and mortality in newborn infants. However, despite the many remarkable achievements in this field, major questions remain unanswered. The goal of this review is to summarize our present understanding of surfactant homeostatic mechanisms and highlight important knowledge gaps in molecular pathways involved in surfactant synthesis, secretion, recycling, and degradation. This focus excludes discussion of the role of surfactant in innate lung defense, and the reader is referred to several excellent reviews of this topic (46, 57, 60, 109).

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