Hyaluronan in the Pulmonary Alveolus and Interstitium

Hyaluronan (HA); a repeating polymer of N-acetylglucosamine linked β1,4 to glucuronic acid, which is linked β1,3 to the next N-acetylglucosamine; is ubiquitous in soft tissues. It is increased when more open structures are required for cell migration as in embryogenesis and during repair. In the lung, the HA content correlates with extravascular water. HA is present in all major structural components of the lung, including alveoli, bronchi, pleura and blood vessels, and is synthesized by the following lung cells: fibroblasts, alveolar macrophages, mesothelial, endothelial and epithelial cells, including the Type II epithelial cells in the alveolar wall. HA is obvious around larger blood vessels and in alveolar macrophages in experiments using a biotinylated hyaluronanbinding protein (HABP) as a probe. The increased synthesis of HA in the lung after bleomycin injury involves lung fibroblasts and alveolar macrophages. The macrophages become activated and release factors that stimulate HA production by lung fibroblasts (16). Impaired removal of HA by alveolar macrophages also contributes to the accumulation of HA after bleomycin injury. The cell receptor for HA, CD44, is critical for the resolution of the inflammation generated as a result of the bleomycin injury. HA has many potential functions in the alveolus and interstitium, in addition to the ones already proven. Various studies designed to clarify these roles are already underway in many laboratories. As mentioned previously, the tools of molecular biology will enable the investigators to ask specific questions about HA synthases and hyaluronidases.