Partial degradation products of sodium hyaluronate produced by the action of testicular hyaluronidase induced an angiogenic response (formation of new blood vessels) on the chick chorioallantoic membrane. Neither macromolecular hyaluronate nor exhaustively digested material had any angiogenic potential. Fractionation of the digestion products established that the activity was restricted to hyaluronate fragments between 4 and 25 disaccharides in length.

https://science.sciencemag.org/content/sci/228/4705/1324.full.pdf

Angiogenesis induced by degradation products of hyaluronic acid.

Target specific and long-acting delivery of protein, peptide, and nucleotide therapeutics using hyaluronic acid derivatives.

The hyaluronan receptor belongs to the polymorphic family of CD44 glycoproteins, which have been implicated in a variety of cellular functions including adhesion to hyaluronan and collagen, the binding of lymphocytes to high endothelial cells during extravasation, and conferring metastatic potential to carcinoma cells. Here, we demonstrate that the receptor also participates in the uptake and degradation of hyaluronan by both transformed fibroblasts (SV-3T3 cells) and alveolar macrophages. These cells were incubated with isotopically labeled hyaluronan for various periods of time, and the extent of degradation was determined by either molecular-sieve chromatography or centrifugation through Centricon 30 microconcentrators. The macrophages degraded the hyaluronan at a faster rate than the SV-3T3 cells, which may reflect the fact that they contained a greater number of receptors. More importantly, in both cell types, the degradation of hyaluronan was specifically blocked by antibodies directed against the receptor. However, the receptor by itself did not have the ability to degrade hyaluronan, since preparations of SV-3T3 membranes containing the receptor did not break down hyaluronan. Subsequent experiments revealed that macrophages can internalize fluorescein-tagged hyaluronan, and this process was blocked by antibodies against the receptor. Furthermore, the subsequent degradation of hyaluronan was inhibited by agents that block the acidification of lysosomes (chloroquine and NH4Cl). Thus, the most likely explanation for these results is that the receptor mediates the uptake of hyaluronan into the cell where it can be degraded by acid hydrolases in lysosomes. The ability of cells expressing the receptor to degrade hyaluronan may be important during tissue morphogenesis and cell migration.

/pdf/the-hyaluronan-receptor-cd44-participates-in-the-uptake-and-5dcnnmg8sb.pdf

The hyaluronan receptor (CD44) participates in the uptake and degradation of hyaluronan.

The endothelial cell glycocalyx influences blood flow and presents a selective barrier to movement of macromolecules from plasma to the endothelial surface. In the hamster cremaster microcirculatio...

Permeation of the luminal capillary glycocalyx is determined by hyaluronan

A Model for the Role of Hyaluronic Acid and Fibrin in the Early Events during the Inflammatory Response and Wound Healing

Endothelial cells are a site of uptake and degradation of hyaluronic acid in the liver.

Part of the hyaluronic acid (HA) synthesized in peripheral tissues enters the blood circulation through the lymph. It is rapidly taken up by the endothelial cells in the liver (half-life in blood is 2.5–5.5 minutes) and degraded. Pure primary cultures of liver endothelial cells were obtained by a newly developed technique and used to follow the metabolism of the polysacharide. At 7°C the cells exhibit a saturable binding of HA indicating a specific receptor for the polysaccharide on the cell surface. At 37°C the HA is effectively endocytosed and degraded to acetate and lactate. A radioassay specific for HA and sensitive in the nanogram range has been developed to follow the concentration of HA in serum. The normal level in man is 10 to l00ug/l. Elevated serum levels of HA are seen in liver cirrhosis, rheumatoid arthritis and scleroderma indicating that both an impaired catabolism in the liver and an increased synthesis in the peripheral tissues can modify the HA level.

J. Robert E. Fraser

Papers

Endothelial cells are a site of uptake and degradation of hyaluronic acid in the liver.

The Catabolic Fate of Hyaluronic Acid

Minisymposium: Hyaluronan: clinical perspectives of an old polysaccharide: Introduction