Pulmonary Surfactant Surface Tension Influences Alveolar Capillary Shape and Oxygenation

Alveolar capillaries are located in close proximity to the alveolar epithelium and beneath the surfactant film. We hypothesized that the shape of alveolar capillaries and accompanying oxygenation are influenced by surfactant surface tension in the alveolus. To prove our hypothesis, surfactant surface tension was regulated by conditional expression of surfactant protein (SP)-B in Sftpb−/− mice, thereby inhibiting surface tension–lowering properties of surfactant in vivo within 24 hours after depletion ofSftpb. Minimum surface tension of isolated surfactant was increased and oxygen saturation was significantly reduced after 2 days of SP-B deficiency in association with deformation of alveolar capillaries. Intravascularly injected 3.2-μm-diameter microbeads through jugular vein were retained within narrowed pulmonary capillaries after reduction of SP-B. Ultrastructure studies demonstrated that the capillary protrusion typical of the normal alveolar–capillary unit was reduced in size, consistent with altered pulmonary blood flow. Pulmonary hypertension and intrapulmonary shunting are commonly associated with surfactant deficiency and dysfunction in neonates and adults with respiratory distress syndromes. Increased surfactant surface tension caused by reduction in SP-B induced narrowing of alveolar capillaries and oxygen desaturation, demonstrating an important role of surface tension–lowering properties of surfactant in the regulation of pulmonary vascular perfusion. Keywords: surfactant protein-B, transgenic mice, pulmonary blood flow, acute respiratory distress syndrome, pulmonary vascular perfusion Pulmonary surfactant is a complex mixture of lipids and associated proteins that are required for formation and stability of surfactant film in the alveolus. After secretion from type II epithelial cells, surfactant forms a lipid rich film that covers the entire alveolar surface, reducing surface tension at the air/liquid interface from 70 mN/m to near 0 mN/m (1). The reduction of alveolar surface tension is required for the maintenance of alveolar surface area, upon which respiration depends. Surfactant function requires the presence of surfactant protein (SP)-B, a small hydrophobic protein that is tightly associated with surfactant phospholipids in the alveolus (1, 2). In humans and mice, SP-B deficiency or mutations in SFTPB cause respiratory failure and death in adults and neonates (3–5). Conditional reduction of SP-B for 4 days in adult mice causes respiratory failure associated with abnormal high surface tension of the surfactant present in bronchoalveolar lavage fluid (BALF) (6–8). This conditional SP-B mouse provides a useful model for study of the influence of surface tension on lung structure, function, and inflammation in adult lung in vivo. The loss of surfactant surface activity influences the shape and function of cells beneath the surfactant film. For example, reduction in SP-B increases the surface tension of surfactant, influencing both cell shape and phagocytic activity of alveolar macrophages in vivo, providing support for the concept that surface tension influences cell shape and function in the alveolus (9). Acute lung injury is a common cause of mortality and morbidity associated with high surface tension in the alveolus as a result of surfactant deficiency and dysfunction in both children and adults (10, 11). Concentrations of SP-B in BALF from patients with acute respiratory distress syndrome were decreased to 20 to 50% of normal (11). Pulmonary hypertension and intrapulmonary shunting is commonly associated with respiratory distress syndrome in neonates and adults, resulting in the impairment of ventilation perfusion or disrupting normal gas exchange. The alveolar capillary unit consists of a region composed of both interstitial and epithelial components. In addition to alveolar pressure, other capillary compressive forces, including alveolar surface tension and tension in connective tissue fibers (12, 13), must be overcome for recruitment to occur. Because of the close apposition of the alveolar cell surfaces and epithelial component of vessels of the microcirculation, changes in surface tension may influence capillary blood flow via transmitted forces. In the present study, we sought to test the hypothesis that decreased activity of pulmonary surfactant alters alveolar capillary shape that in turn influences alveolar capillary blood flow and gas exchange in vivo. For these studies, a mouse model in which the expression of SP-B in respiratory epithelial cells was conditionally controlled in vivo was used.

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