Differences in hyaluronic acid-mediated functions and signaling in arterial, microvessel, and vein-derived human endothelial cells

Hyaluronic acid (HA), a nonsulfated glycosaminoglycan, regulates cell adhes ion and migration. Small HA fragments (3-25 disaccharide units) induce neov ascularization, We investigated the effect of HA and a HA fragment (10-15 d isaccharide units, F1) on primary human endothelial cells (ECs). Human pulm onary ECs (HPAEC) and lung microvessel ECs (HMVEC-L) bound HA (K-d similar to 1 and 2.3 nM, respectively) and expressed 17,780 and 16,690 HA binding s ites, respectively. Both ECs showed HA-mediated cell adhesion; however, HMV EC-L was 1.5-fold better. Human umbilical vein ECs neither bound HA nor sho wed HA-mediated adhesion. All three ECs expressed CD44 (similar to 110 kDa) . The expression of receptor for HA-mediated motility (RHAMM) (similar to 8 0 kDa) was the highest in HMVEC-L, followed by HPAEC and human umbilical ve in ECs, RHAMM, not CD44, bound HA in all three ECs. Fl was better than HA a nd stimulated a 2.5- and 1.8-fold mitogenic response in HMVEC-L and HPAEC, respectively. Both HA and F1 induced tyrosine phosphorylation of p125(FAK), paxillin, and p42/44 ERK in HMVEC-L and HPAEC, which was blocked by an ant i-RHAMM antibody. These results demonstrate that RHARIM is the functional H A receptor in primary human ECs. Heterogeneity exists among primary human E Cs of different vascular origins, with respect to functional HA receptor ex pression and function.