HYALURONAN METABOLISM IN RAT TAIL SKIN FOLLOWING BLOCKAGE OF THE LYMPHATIC cmCULATION

This study was undertaken to explore the effects of lymphatic blockage on the metabolism of hyaluronan in the skin. In initial experiments, PH] hyaluronan was injected subcutaneously into the tail skin of rats that either had no surgical intervention (control) or into those that had their lymphatic drainage blocked two hours earlier (acute lymphedema) or after the lymphatics had been blocked for three months (chronic lymphedema). The removal of tritiated hyaluronan from the injection sites was determined by the appearance ofPH] in the plasma. The results showed that the clearance of injected hyaluronan was delayed in rats with lymphatic blockage. The halflife of injected hyaluronan in the controls was -70-75 hr, compared with -105-110 hr in the lymph blocking rats. The levels of radioactivity in the plasma from rats with both acute and chronically blocked lymphatics were lower than that of control rats during the entire follow up period. In addition, biochemical analysis revealed that there was a significant increased amount of hyaluronan in the tail skin three months after lymphatic blocking. These results suggest that lymph absorption is an important factor in the transport of hyaluronan from the interstitium. Blockage of regional draining lymphatics likely impairs the catabolism of hyaluronan, which stagnates in skin tissue. It is known that lymphatic transport plays a major role in the metabolism of macromolecules of the interstitial matrix and, in particular, plasma proteins such as albumin. However, little is known about the role of lymphatics in the turnover of the polysaccharide components of the matrix, such as hyaluronan. The interstitium has been considered a static structure in which matrix component are catabolized locally. This view has been modified because at least one of its major components hyaluronan, a large macromolecule (MW 1 X 106Kd) shares the same catabolic pathway as albumin, being drained away from tissues through lymphatic pathways (1). Hyaluronan is partly metabolized in lymph nodes and enters the general circulation and is rapidly degraded in the liver. Because the lymph circulation is the main pathway for transport of hyaluronan from tissues, an impaired lymph circulation should not only promote stagnation of interstitial fluid, but also alter the metabolism of hyaluronan. In our previous study (2), the hyaluronan content was significantly increased in the tissue fluid of patients with peripheral lymphedema compared with tissue fluid in healthy limbs. In order to clarify the influence of lymph flow on hyaluronan metabolism in the skin, we surgically blocked the lymphatic network of rat tail skin and then injected tritium Permission granted for single print for individual use. Reproduction not permitted without permission of Journal LYMPHOLOGY . labeled hyaluronan subcutaneously either the same day or three months after operation. The specific radioactivity in blood was measured at specific time intervals after injection. The results showed for the first time that the turnover of hyaluronan was greatly impaired by damage to the lymphatic vasculature. MATERIALS AND METHODS