Pulmonary Surfactant Surface Tension Influences Alveolar Capillary Shape and Oxygenation

Abstract

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 2/2 mice, thereby inhibiting surface tension-lowering properties of surfactant in vivo within 24 hours after depletion of Sftpb. 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-mmdiameter 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...

Antisickling fetal hemoglobin reduces hypoxia-inducible factor-1α expression in normoxic sickle mice: microvascular implications

“…These values are comparable with %SpO 2 values reported for normoxic mouse (30). Previous studies have shown that %SpO 2 is a valid predictor of %hemoglobin oxygen saturation (%HbO 2 ) as it shows high correlation with %HbO 2 (3,40,45).…”

Surfactant treatment before first breath for respiratory distress syndrome in preterm lambs: comparison of a peptide-containing synthetic lung surfactant with porcine-derived surfactant

“…In agreement with our findings, the researchers also described “uncoupling” between sustained improved oxygenation and lung mechanics in lucinactant-treated animals. They suggested that the uncoupling is due to the presence of SP-B or SP-B-mimicking peptide, KL4, in the surfactants, which support alveolar capillary shape by reducing surface tension, thereby improving pulmonary blood flow and shunt 35. Our study showed uncoupling between C dyn and oxygenation and calculated intrapulmonary shunt, favoring the Synsurf-treated animals over that of Curosurf®- and saline-treated lambs.…”

Leptin does not influence surfactant synthesis in fetal sheep and mice lungs

“…Phosphorus in extracted lipid from BALF and lung homogenate was analyzed (17) for total phospholipid. Surfactant proteins (SP) in BALF containing 50 g of protein was quantified by Western blot analyses using rabbit anti-bovine SP-A, SP-B, and SP-C (Chemicon International, Temecula, CA) and normalized to ␤-actin in the sample (25). The right upper lobe was inflation-fixed at 30 cmH 2O for morphology.…”

“…Low surface tension is critical for gas exchange, alveolar capillary blood flow (25), and alveolar macrophage function of phagocytosis (1). In the fetal lung, the synthesis of pulmonary surfactant dramatically increases at late gestation to prepare for transition to air breathing at birth.…”