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J. Biol. Chem., Vol. 275, Issue 36, 27641-27649, September 8, 2000
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From the Departments of Hyaluronic acid (HA), a nonsulfated
glycosaminoglycan, regulates cell adhesion and migration. Small HA
fragments (3-25 disaccharide units) induce neovascularization. We
investigated the effect of HA and a HA fragment (10-15 disaccharide
units, F1) on primary human endothelial cells (ECs). Human pulmonary
ECs (HPAEC) and lung microvessel ECs (HMVEC-L) bound HA
(Kd ~1 and 2.3 nM, respectively) and
expressed 17,780 and 16,690 HA binding sites, respectively. Both ECs
showed HA-mediated cell adhesion; however, HMVEC-L was 1.5-fold better.
Human umbilical vein ECs neither bound HA nor showed HA-mediated
adhesion. All three ECs expressed CD44 (~110 kDa). The expression of
receptor for HA-mediated motility (RHAMM) (~80 kDa) was the highest
in HMVEC-L, followed by HPAEC and human umbilical vein ECs. RHAMM, not
CD44, bound HA in all three ECs. F1 was better than HA and stimulated a
2.5- and 1.8-fold mitogenic response in HMVEC-L and HPAEC,
respectively. Both HA and F1 induced tyrosine phosphorylation of
p125FAK, paxillin, and p42/44 ERK in HMVEC-L and HPAEC,
which was blocked by an anti-RHAMM antibody. These results demonstrate
that RHAMM is the functional HA receptor in primary human ECs.
Heterogeneity exists among primary human ECs of different vascular
origins, with respect to functional HA receptor expression and function.
Differences in Hyaluronic Acid-mediated Functions and Signaling
in Arterial, Microvessel, and Vein-derived Human Endothelial Cells*
§¶ and
Urology and § Cell
Biology and Anatomy, University of Miami School of Medicine,
Miami, Florida 33101
*
This work was supported by Grant 9701759 from the American
Heart Association Florida Affiliate.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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