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© The Rockefeller University Press, 0021-9525/1999//789 $5.00
The Journal of Cell Biology, Volume 144, Number 4, , 1999 789-801


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LYVE-1, a New Homologue of the CD44 Glycoprotein, Is a Lymph-specific Receptor for Hyaluronan



Suneale Banerji*, Jian Ni{ddagger}, Shu-Xia Wang{ddagger}, Steven Clasper*, Jeffrey Su{ddagger}, Raija Tammi§, Margaret Jones||, and David G. Jackson*

* University of Oxford, Molecular Immunology Group, Nuffield Department of Medicine and || Department of Cellular Science, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom; § Department of Anatomy, University of Kuopio, FIN-70211 Kuopio, Finland; and {ddagger} Human Genome Sciences, Inc., Rockville, Maryland 20850

The extracellular matrix glycosaminoglycan hyaluronan (HA) is an abundant component of skin and mesenchymal tissues where it facilitates cell migration during wound healing, inflammation, and em- bryonic morphogenesis. Both during normal tissue homeostasis and particularly after tissue injury, HA is mobilized from these sites through lymphatic vessels to the lymph nodes where it is degraded before entering the circulation for rapid uptake by the liver. Currently, however, the identities of HA binding molecules which control this pathway are unknown. Here we describe the first such molecule, LYVE-1, which we have identified as a major receptor for HA on the lymph vessel wall. The deduced amino acid sequence of LYVE-1 predicts a 322-residue type I integral membrane polypeptide 41% similar to the CD44 HA receptor with a 212-residue extracellular domain containing a single Link module the prototypic HA binding domain of the Link protein superfamily. Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA. However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels. Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.

Key Words: hyaluronic acid • endothelium, lymphatic • DNA, complementary • receptors, cell surface • recombinant fusion proteins



Abbreviations used in this paper: bHABC, biotinylated HA-binding complex; EST, expression sequence tag; HA, hyaluronan; HUVEC, human umbilical vein endothelial cells; LEC, liver endothelial cell; LYVE-1, lymphatic vessel endothelial HA receptor 1; RHAMM, receptor for hyaluronan mediated motility; vWF, von Willebrand factor.



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