Turnover and metabolism of hyaluronan.

The highest concentrations of hyaluronan occur in synovial fluid, vitreous body, skin and certain specialized tissues such as umbilical cord and rooster comb, during fetal development, and in tissue repair and regeneration. The largest amounts are found in the intercellular matrix of skin and musculoskeletal tissues. Turnover in the bloodstream is normally in the range of 0.3-1.0 microgram min-1/kg body weight. Circulating hyaluronan is mostly derived from lymph. Lymph nodes may nevertheless extract as much as 80-90% from peripheral lymph before it can reach the bloodstream. Turnover in peripheral tissues may be effected by degradation in situ, or by transfer into lymph by diffusion or hydrodynamic forces. Hyaluronan is firmly bound in specific association with cells or binding proteins but much of it exists in freely mobilized compartments with a half-life of two days or less, and it is metabolized after transport elsewhere. Metabolic degradation of hyaluronan is principally intracellular and relies on uptake by a receptor which, in contrast with other hyaluronan-binding structures, also binds chondroitin sulphate. It is suggested that this dual specificity may be primarily associated with metabolic degradation of hyaluronan. Uptake and metabolism are primarily effected in liver and lymph node by endothelial cells lining the sinusoids of each. Further studies indicate that in lymph nodes and in spleen, macrophage-like cells intertwined with the endothelial cells also take up hyaluronan. The metabolic cycle from polymer to monosaccharides, acetate and beyond can be completed in vivo within 10 minutes.