Hyaluronan: its nature, distribution, functions and turnover.

Hyaluronan is a polysaccharide found in all tissues and body fluids of vertebrates as well as in some bacteria. It is a linear polymer of exceptional molecular weight, especially abundant in loose connective tissue. Hyaluronan is synthesized in the cellular plasma membrane.

Hyaluronan in human cerebrospinal fluid.

We studied the concentration of hyaluronan in cerebrospinal fluid (CSF) in various diseases and attempted to define its reference interval. A radioassay utilizing cartilage proteins with affinity for hyaluronan was used in determining the concentration of 200 lumbar and 27 ventricular CSF specimens and 11 brain cyst fluids. Molecular weight distributions were determined by gel chromatography and localization in brain tissue by histochemistry.

Serum hyaluronan as a disease marker.

Hyaluronan is a connective tissue polysaccharide which has also been found in blood serum in concentrations < 100 micrograms/L (average 30-40 micrograms/L in middle-aged persons). The serum level is regulated by the influx of the polysaccharide from the tissues via lymph and its receptor-mediated clearance by liver endothelial cells. Markedly high serum levels are noted in certain liver diseases, especially in patients with cirrhosis, when the clearance is impaired.

The structure and function of hyaluronan: An overview.

Hyaluronan is a major component of synovial tissue and fluid as well as other soft connective tissues. It is a high-Mr polysaccharide which forms entangled networks already at dilute concentrations (< 1 mg/mL) and endows its solutions with unique rheological properties. Physiological functions of hyaluronan (lubrication, water homeostasis, macromolecular filtering, exclusion, etc.

Effect of increased interstitial fluid flux on fractional catabolic rate of high molecular weight [3H]hyaluronan injected in rabbit skin.

The removal rate of high molecular weight (M(r) 3 x 10(6) [3H]hyaluronan has been measured in rabbit paw skin in control and during increased local venous pressure induced by ligation of the femoral vein. The increased venous pressure resulted in a 20% increase of interstitial volume at 4 h after ligation, a value which relates to at least a doubling of lymph flow, i.e.

Hyaluronan injected in the anterior chamber of the eye is catabolized in the liver.

Catabolism of hyaluronan was studied by injecting hyaluronan (M(r) 200,000) labelled with [125I]-tyramine cellobiose, ([125I]-TC), into the anterior chamber of the rabbit eye. After endocytosis [125I]-TC accumulates in cells, allowing localization of the site of catabolism. When 0.

Turnover of hyaluronan in the microcirculation.

Hyaluronan in skin, lung, and intestine turns over within a few days and catabolism takes place locally in the tissues, in local lymph nodes, and in the liver. Hyaluronan will affect microcirculatory exchange through its influence on interstitial volume exclusion, hydraulic conductivity, and diffusivity of macromolecules. Prolonged increase in interstitial fluid flux in intestine has been shown to reduce the hyaluronan content, which in turn increases hydraulic conductivity and diffusivity of macromolecules.

Turnover of hyaluronan in the rabbit pleural space.

Hyaluronan influences lung fluid balance. The clearance of lung hyaluronan by way of the pulmonary lymphatics and the pleural space is increased when fluid flux into the interstitium is increased. The purpose of this study was to determine the rate at which hyaluronan is removed from the pleural space.

Concentration and turnover of intraperitoneal hyaluronan during inflammation.

Aseptic peritonitis was induced in rabbits by intraperitoneal injection of irritating agents, mainly starch suspensions. The inflammatory response was followed in the peritoneal lavage fluid by cell counts (average increase about 800-fold the first day) and hyaluronan concentration (average increase about 200-fold on the second and third days). The turnover rate of hyaluronan was studied by injecting tritium-labeled hyaluronan intraperitoneally and by following the appearance of tritiated water in serum.

Catabolism of hyaluronan in the knee joint of the rabbit.

Catabolism of hyaluronan was studied by injecting hyaluronan labelled with [125I]-tyramine cellobiose ([125I]-TC) into knee joints of rabbits. After endocytosis [125I]-TC remains intracellularly allowing localization of the site of catabolism. At 6 hours after injection 63% could be recovered in and around the joint, while at 48 hours 32% remained locally.

Catabolism of hyaluronan in rabbit skin takes place locally, in lymph nodes and liver.

The catabolism of hyaluronan has been studied by injecting hyaluronan, labelled with 125I-tyramine cellobiose (125I-TC), subcutaneously into the hindpaw of rabbits. Following endocytosis, 125I-TC remains in the cells at the site of uptake, allowing localization of the site of catabolism. At 6 h after subcutaneous injection, 65% of the injected radioactivity was recovered.

Turnover of hyaluronan in synovial joints: elimination of labelled hyaluronan from the knee joint of the rabbit.

After the injection of [3H]acetyl-labelled hyaluronan into normal rabbit knee joints, about 90% of its isotope content was ultimately accounted for as 3H2O. The rate of elimination of hyaluronan from synovial fluid was therefore estimated from changes in the level of 3H2O in plasma. The half-life of plasma 3H2O was 6.

Removal rate of [3H]hyaluronan injected subcutaneously in rabbits.

Hyaluronan is an important constituent of the extracellular matrix in skin, and recent studies suggest that there is a pool of easily removable ("free") hyaluronan drained by lymph. The removal rate of free hyaluronan in skin was measured from the elimination of [3H]hyaluronan, injected subcutaneously in 13 rabbits. The removal of radioactivity was determined from appearance of 3H in plasma.

Disappearance of concentrated hyaluronan from the anterior chamber of monkey eyes.

The removal of hyaluronan (HYA) from the primate eye has received attention due to the use of the polymer in ophthalmic surgery. The turnover of concentrated HYA injected into the anterior chamber of 12 cynomolgus monkeys was therefore studied using a technique earlier described for rabbits. The technique is based on the observation that when HYA labelled with tritium in the acetyl group leaves the eye and enters the circulation it is rapidly taken up by the liver and degraded to tritiated water.

The diurnal variation of serum hyaluronan in health and disease.

The variation of the serum concentration of hyaluronan during the day and between days has been investigated. In a group of healthy volunteers, the mean hyaluronan level was very stable over time except for a moderate but significant elevation after rising from bed in the morning. Patients with rheumatoid arthritis showed markedly increased hyaluronan concentrations 0.

An experimental technique to study the turnover of concentrated hyaluronan in the anterior chamber of the rabbit.

An experimental technique to study the turnover of hyaluronan in the anterior chamber in single animals has been developed. It is based on the fact that circulating hyaluronan labelled with tritium in the acetyl group is rapidly taken up by the liver and degraded to tritiated water. 3H-labelled hyaluronan was mixed with high concentration, high molecular weight hyaluronan (Healon) and injected into the anterior chamber of rabbits.

Urinary excretion of hyaluronan in man.

A specific assay for hyaluronan (hyaluronic acid) has been applied to the determination of the polysaccharide in urine. The excretion in 22 healthy subjects was 330 micrograms/24 h (SD 77). The excretion was correlated with body weight and was therefore somewhat higher in males than in females.

Concentration and relative molecular mass of hyaluronate in lymph and blood.

Human lymph was collected from patients with leaking lymph vessels after thoracic surgery. Ovine lymph was obtained from the mesenteric, lumbar, popliteal and prescapular lymph ducts by cannulation. The concentration of hyaluronate varied considerably (between 0.

The catabolic fate of hyaluronic acid.

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.

Concentration of sodium hyaluronate in serum.

A radioassay for sodium hyaluronate using high-affinity binding protein from bovine cartilage has been modified for serum analysis. The accuracy of the method was checked by isotope dilution experiments and by recovery studies with exogenous hyaluronate. The between-assay standard deviation in the determination is 15-20%.

Elimination of hyaluronic acid from the blood stream in the human.

The removal of hyaluronic acid (HA) from the blood-stream was studied in four normal human subjects after injection of high molecular weight preparations labelled with 3H in the acetyl position. The plasma half-life of the injected material ranged between 2.5 and 5.

The concentration of hyaluronate in amniotic fluid.

The concentration of sodium hyaluronate has been determined in amniotic fluid by a specific radioassay. It shows a large individual variation. The mean concentration is approximately 20 micrograms/ml at Weeks 16-20 of the gestational period.