TRANSFORMING GROWTH-FACTOR BETA(1)-HYALURONIC ACID INTERACTION

Chick embryo skin fibroblasts release transforming growth factor beta( 1) that is able to modulate glycosaminoglycan synthesis and secretion. When incubated with individual classes of glycosaminoglycans, the fac tor's modulatory activity was altered. To determine whether direct int eractions between transforming growth factor pi and glycosaminoglycans occur, we have assessed the activity of the growth factor after pre-i ncubation with single classes of glycosaminoglycans by assaying its in hibitory effect upon the proliferative response of thymocytes stimulat ed with interleukin-1. Untreated transforming growth factor beta(1) su ppressed the proliferative response of thymocytes to interleukin-1, as did transforming growth factor beta(1) pre-incubated with sulphated g lycosaminoglycans. By contrast, transforming growth factor beta(1) los t its inhibitory capacity when preincubated with high molecular weight hyaluronic acid. Digestion of transforming growth factor beta(1)-hyal uronic acid complex with hyaluronidase released active transforming gr owth factor beta(1), Trypsin degraded transforming growth factor beta( 1) alone, but did not degrade the transforming growth factor beta(1)-h yaluronic acid complex. These results suggest that hyaluronic acid int eracts with transforming growth factor beta(1), thus protecting the fa ctor from tryptic degradation and may be a means of concentrating grow th factor activity.