The properties and turnover of hyaluronan

Hyaluronan (HA) was discovered over 50 years ago but its metabolism and cellular interactions have only recently received detailed attention. HA is synthesized in the plasma membrane by addition of monosaccharides to the reducing terminal. In tissues, it occurs bound to plasma membranes, aggregated with other macromolecules, or as free polysaccharide. Tissue HA enters the bloodstream in significant amounts through the lymph and is rapidly absorbed via a receptor into liver endothelial cells, where degradation follows. HA levels in serum are normally 10-100 micrograms/l, but can be elevated in cirrhosis, rheumatoid arthritis and scleroderma, due either to impaired hepatic uptake or to increased production. Studies on aqueous humour, middle ear secretion, amniotic fluid, lung lavage fluid, urine, skin diseases and cancer have identified other causes of deranged HA metabolism. HA can be visualized on some cell surfaces as a coating impermeable to particulate material. Specific HA binding occurs on lymphoma cell lines, lung macrophages and SV-3T3 cells but, except in synthesis or uptake, the significance of membrane-associated HA is incompletely understood. It has been reported to activate macrophages and granulocytes, protect cells, control cell migration, and cooperate with intercellular matrix in cell detachment; it also plays a central role in growth control, cellular differentiation and tissue morphogenesis.