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LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan.

Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG - J. Cell Biol. (1999)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: University of Oxford, Molecular Immunology Group, Nuffield Department of Medicine, John Radcliff Hospital, Headington, Oxford OX3 9DU, United Kingdom.

ABSTRACT
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 embryonic 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.

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Related in: MedlinePlus

LYVE-1 molecules support HA-mediated binding to  CD44. The capacity of LYVE-1 and CD44 to form ternary complexes with HA was tested using a modification of the HA-binding assay in Fig. 4 B. A shows binding of LYVE-1 Fc and CD33  Fc (control) to HA, presented by immobilized CD44158his protein.  B shows binding of CD44 Fc to HA, presented by immobilized  LYVE-1 Fc or CD33 Fc (control). Bound fusion proteins were  detected with peroxidase-conjugated anti–human IgFc antibody,  or with peroxidase-conjugated CD44 mAb A3D8, respectively,  as described in Materials and Methods. No binding was observed  in the absence of HA (not shown). Data are the mean ± SEM  (n = 3).
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Figure 10: LYVE-1 molecules support HA-mediated binding to CD44. The capacity of LYVE-1 and CD44 to form ternary complexes with HA was tested using a modification of the HA-binding assay in Fig. 4 B. A shows binding of LYVE-1 Fc and CD33 Fc (control) to HA, presented by immobilized CD44158his protein. B shows binding of CD44 Fc to HA, presented by immobilized LYVE-1 Fc or CD33 Fc (control). Bound fusion proteins were detected with peroxidase-conjugated anti–human IgFc antibody, or with peroxidase-conjugated CD44 mAb A3D8, respectively, as described in Materials and Methods. No binding was observed in the absence of HA (not shown). Data are the mean ± SEM (n = 3).

Mentions: Finally, we looked for evidence that leukocytes adhere to HA presented by LYVE-1 present on the lymph vessel wall. Our initial attempts to demonstrate such adhesion using CD44 transfected Namalwa B lymphoma cells and frozen sections of gut lymphatics in Stamper-Woodruff type assays were difficult to interpret, because of the high levels of binding to HA within the surrounding parenchyma (not shown). As an alternative, we tested the ability of LYVE-1 Fc immobilized on plastic microtiter dishes to support HA-mediated binding to CD44. As shown in Fig. 10, LYVE-1 indeed supported HA-mediated binding of CD44, regardless of the order used for primary presentation or secondary HA binding. In conclusion, our results indicate that LYVE-1, in addition to binding HA within the lymphatics, may also bind HA-coated lymphocytes in transit to the lymph nodes.


LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan.

Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG - J. Cell Biol. (1999)

LYVE-1 molecules support HA-mediated binding to  CD44. The capacity of LYVE-1 and CD44 to form ternary complexes with HA was tested using a modification of the HA-binding assay in Fig. 4 B. A shows binding of LYVE-1 Fc and CD33  Fc (control) to HA, presented by immobilized CD44158his protein.  B shows binding of CD44 Fc to HA, presented by immobilized  LYVE-1 Fc or CD33 Fc (control). Bound fusion proteins were  detected with peroxidase-conjugated anti–human IgFc antibody,  or with peroxidase-conjugated CD44 mAb A3D8, respectively,  as described in Materials and Methods. No binding was observed  in the absence of HA (not shown). Data are the mean ± SEM  (n = 3).
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Related In: Results  -  Collection

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Figure 10: LYVE-1 molecules support HA-mediated binding to CD44. The capacity of LYVE-1 and CD44 to form ternary complexes with HA was tested using a modification of the HA-binding assay in Fig. 4 B. A shows binding of LYVE-1 Fc and CD33 Fc (control) to HA, presented by immobilized CD44158his protein. B shows binding of CD44 Fc to HA, presented by immobilized LYVE-1 Fc or CD33 Fc (control). Bound fusion proteins were detected with peroxidase-conjugated anti–human IgFc antibody, or with peroxidase-conjugated CD44 mAb A3D8, respectively, as described in Materials and Methods. No binding was observed in the absence of HA (not shown). Data are the mean ± SEM (n = 3).
Mentions: Finally, we looked for evidence that leukocytes adhere to HA presented by LYVE-1 present on the lymph vessel wall. Our initial attempts to demonstrate such adhesion using CD44 transfected Namalwa B lymphoma cells and frozen sections of gut lymphatics in Stamper-Woodruff type assays were difficult to interpret, because of the high levels of binding to HA within the surrounding parenchyma (not shown). As an alternative, we tested the ability of LYVE-1 Fc immobilized on plastic microtiter dishes to support HA-mediated binding to CD44. As shown in Fig. 10, LYVE-1 indeed supported HA-mediated binding of CD44, regardless of the order used for primary presentation or secondary HA binding. In conclusion, our results indicate that LYVE-1, in addition to binding HA within the lymphatics, may also bind HA-coated lymphocytes in transit to the lymph nodes.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: University of Oxford, Molecular Immunology Group, Nuffield Department of Medicine, John Radcliff Hospital, Headington, Oxford OX3 9DU, United Kingdom.

ABSTRACT
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 embryonic 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.

Show MeSH
Related in: MedlinePlus