The lymphatic vasculature forms a second circulatory system that drains extracellular fluid from the tissues and provides an exclusive environment in which immune cells can encounter and respond to foreign antigen. Recently a number of interesting molecules have been identified that may be exploited as markers for lymphatic endothelium, including the hyaluronan receptor LYVE1, PALE, VEGFR3, and podoplanin. LYVE1 has been identified as a major receptor for HA (extracellular matrix glycosaminoglycan hyaluronan) on the lymph vessel wall. The deduced amino acid sequence of LYVE1 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 LYVE1 molecule binds both soluble and immobilized HA. However, unlike CD44, the LYVE1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels. Hence, LYVE1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.
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