The Role of Hyaluronan in the Pulmonary Alveolus

Abstract The duplex nature of the lining of the pulmonary alveolus has long been appreciated. It appears that surfactant is present at the interface with air where it prevents the collapse of the alveolus by lowering surface tension and that the surfactant rests on an aqueous subphase. This subphase has enough structure to form a smooth, continuous surface over the projections of the epithelial cells and because of its hydrophilic nature it attracts the polar heads of surfactant phospholipids. The chemical composition of the subphase has not been addressed. Type II cells in the wall of the alveolus are specialized to produce surfactant and they also secrete hyaluronan (hyaluronic acid) into the subphase. In solution, molecules of hyaluronan appear to be flexible coils which self-aggregate. The resulting solutions are quite viscous and exhibit non-Newtonian behavior. Hyaluronan binds to cell surface receptors and to proteins in the extracellular matrix. The networks formed with self-aggregated hyaluronan with or without proteins create gels whose properties depend largely upon the molecular weight of the hyaluronan and its concentration. Hyaluronan is also known to interact with phospholipids and has hydrophobic regions which could bind to the hydrophobic surfactant proteins B and C. The working hypothesis presented herein states that hyaluronan interacts with itself and with proteins in the subphase to form a hydrophilic gel. At the epithelial cell layer the components are concentrated due to tethered HA molecules and the gel smooths over cell projections. At the air interface the components are so dilute that a layer which is essentially water is present. The surfactant phospholipids spread on the water. Direct interactions of HA and surfactant phospholipids may also occur and contribute to the stability of the surfactant layer.