AnnalsATS Volume 12 Number 5| May 2015

Abstract
Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigeninduced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocytemacrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis.Here, we briefly reviewthe composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications.

Physiology June 1, 2010 vol. 25 no. 3

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).

Eur Respir J 1999; 13: 1455-1476

Pulmonary surfactant is a complex and highly surface active material composed of lipids and proteins which is found in the fluid lining the alveolar surface of the lungs. Surfactant prevents alveolar collapse at low lung volume, and preserves bronchiolar patency during normal and forced respiration (biophysical functions). In addition, it is involved in the protection of the lungs from injuries and infections caused by inhaled particles and micro-organisms (immunological, non-biophysical functions). Pulmonary surfactant can only be harvested by lavage procedures, which may disrupt its pre-existing biophysical and biochemical micro-organization. These limitations must always be considered when interpreting ex vivo studies of pulmonary surfactant. A pathophysiological role for surfactant was first appreciated in premature infants with respiratory distress syndrome and hyaline membrane disease, a condition which is nowadays routinely treated with exogenous surfactant replacement. Biochemical surfactant abnormalities of varying degrees have been described in obstructive lung diseases (asthma, bronchiolitis, chronic obstructive pulmonary disease, and following lung transplantation), infectious and suppurative lung diseases (cystic fibrosis, pneumonia, and human immunodeficiency virus), adult respiratory distress syndrome, pulmonary oedema, other diseases specific to infants (chronic lung disease of prematurity, and surfactant protein-B deficiency), interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis, and hypersensitivity pneumonitis), pulmonary alveolar proteinosis, following cardiopulmonary bypass, and in smokers. For some pulmonary conditions surfactant replacement therapy is on the horizon, but for the majority much more needs to be learnt about the pathophysiological role the observed surfactant abnormalities may have.