The influence of sulfated polysaccharides on the circulating levels of hyaluronan.

When chondroitin sulfate (CS) or dextran sulfate (DxS) was administered intravenously in rats the levels of circulating hyaluronan (HA) rapidly increased. 70 min after injection the levels were found to be about 10-20 times the initial values. Saline injections were without effect on HA levels. CS given intraperitoneally was found to give prolonged blocking of liver uptake of labeled HA and increased endogenous serum HA to about 10 times the initial level at 180 min. HA excretion in urine was dramatically increased by CS given intravenously, intraperitoneally as well as subcutaneously. Size-exclusion chromatography showed a mean MW of the circulating HA of around 50 kDa while urinary HA had a mean MW of about 10 kDa. Circulating HA has previously been shown to be very effectively cleared via receptor mediated endocytosis by reticuloendothelial cells, primarily liver endothelial cells. As CS and DxS bind to the same receptors and inhibits HA clearance, the effects of sulfated polysaccharides on inflammatory conditions and angiogenesis might be via HA, previously shown to affect these processes. Such a mechanism could also explain increased HA levels as a secondary event to increased CS and other sulfated biological polysaccharides in some physiological and pathological conditions.