CIRCULATING HYALURONAN, CHONDROITIN SULFATE AND DEXTRAN SULFATE BIND TO A LIVER RECEPTOR THAT DOES NOT RECOGNIZE HEPARIN

Chondroitin sulphate, injected intravenously into rats and given prior to intravenous I-125-labelled hyaluronan with a mean Mw of about 400 kDa, was shown to inhibit the rapid receptor-mediated uptake of hyalur onan by the liver. The labelled hyaluronan that remained in the circul ation was shown, by size exclusion chromatography of serum and urine, to be rapidly degraded down to fragments of lower Mw and filtered out into the urine and tissues. When the uptake of I-125-hyaluronan was in hibited by unlabelled hyaluronan, only very low degradation and urinar y excretion were found. Liver uptake could also be inhibited by dextra n sulphate but not by heparin. Unlabelled hyaluronan could inhibit the liver uptake of labelled chondroitin sulphate but not labelled hepari n. Unlabelled chondroitin sulphate and dextran sulphate inhibited cell association of labelled hyaluronan to liver endothelial cells in cult ure more effectively than unlabelled hyaluronan. Our data show that th e liver hyaluronan receptors also recognize and effectively bind chond roitin sulphate and dextran sulphate but not heparin and that a hyalur onan-specific saturable degradative mechanism exists in the circulatio n. Such a mechanism could explain why hyaluronan in the general circul ation has a much lower Mw than the hyaluronan in lymph. The results al so indicate that increased hyaluronan levels in serum, and increased u rinary excretion of hyaluronan, may be secondary to increased outflow of chondroitin sulphate from the tissues during some pathological cond itions.