Normal lymphatic development and function in mice deficient for the lymphatic hyaluronan receptor LYVE-1

The hyaluronan receptor LYVE-1 is expressed abundantly on the surfaces of lymphatic vessels and lymph node sinus endothelial cells from early development, where it has been suggested to function both in cell adhesion/transmigration and as a scavenger for hyaluronan turnover. To investigate the physi...

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Vydáno v:Molecular and cellular biology Ročník 27; číslo 2; s. 595
Hlavní autoři: Gale, Nicholas W, Prevo, Remko, Espinosa, Jorge, Ferguson, David J, Dominguez, Melissa G, Yancopoulos, George D, Thurston, Gavin, Jackson, David G
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.01.2007
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ISSN:0270-7306
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Abstract The hyaluronan receptor LYVE-1 is expressed abundantly on the surfaces of lymphatic vessels and lymph node sinus endothelial cells from early development, where it has been suggested to function both in cell adhesion/transmigration and as a scavenger for hyaluronan turnover. To investigate the physiological role(s) of LYVE-1, we generated mice in which the gene for the receptor was inactivated by replacement with a beta-galactosidase reporter. LYVE-1(-/-) mice displayed an apparently normal phenotype, with no obvious alteration in lymphatic vessel ultrastructure or function and no apparent change in secondary lymphoid tissue structure or cellularity. In addition, the levels of hyaluronan in tissue and blood were unchanged. LYVE-1(-/-) mice also displayed normal trafficking of cutaneous CD11c(+) dendritic cells to draining lymph nodes via afferent lymphatics and normal resolution of oxazolone-induced skin inflammation. Finally, LYVE-1(-/-) mice supported normal growth of transplanted B16F10 melanomas and Lewis lung carcinomas. These results indicate that LYVE-1 is not obligatory for normal lymphatic development and function and suggest either the existence of compensatory receptors or a role more specific than that previously envisaged.
AbstractList The hyaluronan receptor LYVE-1 is expressed abundantly on the surfaces of lymphatic vessels and lymph node sinus endothelial cells from early development, where it has been suggested to function both in cell adhesion/transmigration and as a scavenger for hyaluronan turnover. To investigate the physiological role(s) of LYVE-1, we generated mice in which the gene for the receptor was inactivated by replacement with a beta-galactosidase reporter. LYVE-1(-/-) mice displayed an apparently normal phenotype, with no obvious alteration in lymphatic vessel ultrastructure or function and no apparent change in secondary lymphoid tissue structure or cellularity. In addition, the levels of hyaluronan in tissue and blood were unchanged. LYVE-1(-/-) mice also displayed normal trafficking of cutaneous CD11c(+) dendritic cells to draining lymph nodes via afferent lymphatics and normal resolution of oxazolone-induced skin inflammation. Finally, LYVE-1(-/-) mice supported normal growth of transplanted B16F10 melanomas and Lewis lung carcinomas. These results indicate that LYVE-1 is not obligatory for normal lymphatic development and function and suggest either the existence of compensatory receptors or a role more specific than that previously envisaged.
The hyaluronan receptor LYVE-1 is expressed abundantly on the surfaces of lymphatic vessels and lymph node sinus endothelial cells from early development, where it has been suggested to function both in cell adhesion/transmigration and as a scavenger for hyaluronan turnover. To investigate the physiological role(s) of LYVE-1, we generated mice in which the gene for the receptor was inactivated by replacement with a beta-galactosidase reporter. LYVE-1(-/-) mice displayed an apparently normal phenotype, with no obvious alteration in lymphatic vessel ultrastructure or function and no apparent change in secondary lymphoid tissue structure or cellularity. In addition, the levels of hyaluronan in tissue and blood were unchanged. LYVE-1(-/-) mice also displayed normal trafficking of cutaneous CD11c(+) dendritic cells to draining lymph nodes via afferent lymphatics and normal resolution of oxazolone-induced skin inflammation. Finally, LYVE-1(-/-) mice supported normal growth of transplanted B16F10 melanomas and Lewis lung carcinomas. These results indicate that LYVE-1 is not obligatory for normal lymphatic development and function and suggest either the existence of compensatory receptors or a role more specific than that previously envisaged.The hyaluronan receptor LYVE-1 is expressed abundantly on the surfaces of lymphatic vessels and lymph node sinus endothelial cells from early development, where it has been suggested to function both in cell adhesion/transmigration and as a scavenger for hyaluronan turnover. To investigate the physiological role(s) of LYVE-1, we generated mice in which the gene for the receptor was inactivated by replacement with a beta-galactosidase reporter. LYVE-1(-/-) mice displayed an apparently normal phenotype, with no obvious alteration in lymphatic vessel ultrastructure or function and no apparent change in secondary lymphoid tissue structure or cellularity. In addition, the levels of hyaluronan in tissue and blood were unchanged. LYVE-1(-/-) mice also displayed normal trafficking of cutaneous CD11c(+) dendritic cells to draining lymph nodes via afferent lymphatics and normal resolution of oxazolone-induced skin inflammation. Finally, LYVE-1(-/-) mice supported normal growth of transplanted B16F10 melanomas and Lewis lung carcinomas. These results indicate that LYVE-1 is not obligatory for normal lymphatic development and function and suggest either the existence of compensatory receptors or a role more specific than that previously envisaged.
Author Dominguez, Melissa G
Espinosa, Jorge
Jackson, David G
Ferguson, David J
Thurston, Gavin
Yancopoulos, George D
Gale, Nicholas W
Prevo, Remko
Author_xml – sequence: 1
  givenname: Nicholas W
  surname: Gale
  fullname: Gale, Nicholas W
  organization: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom
– sequence: 2
  givenname: Remko
  surname: Prevo
  fullname: Prevo, Remko
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  givenname: Melissa G
  surname: Dominguez
  fullname: Dominguez, Melissa G
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  givenname: George D
  surname: Yancopoulos
  fullname: Yancopoulos, George D
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  givenname: Gavin
  surname: Thurston
  fullname: Thurston, Gavin
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/17101772$$D View this record in MEDLINE/PubMed
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Snippet The hyaluronan receptor LYVE-1 is expressed abundantly on the surfaces of lymphatic vessels and lymph node sinus endothelial cells from early development,...
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SubjectTerms Animals
beta-Galactosidase - genetics
Carcinoma, Lewis Lung - pathology
CD11c Antigen - metabolism
Cell Movement
Dendritic Cells - physiology
Dermatitis, Contact - etiology
Dermatitis, Contact - immunology
Glycoproteins - genetics
Glycoproteins - physiology
Hyaluronic Acid - blood
Hyaluronic Acid - metabolism
Inflammation - chemically induced
Inflammation - immunology
Lymph Nodes - cytology
Lymph Nodes - metabolism
Lymph Nodes - physiology
Lymphatic Vessels - cytology
Lymphatic Vessels - metabolism
Lymphatic Vessels - physiology
Melanoma - pathology
Membrane Transport Proteins
Mice
Mice, Knockout
Neoplasm Transplantation
Oxazolone
Title Normal lymphatic development and function in mice deficient for the lymphatic hyaluronan receptor LYVE-1
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