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.
MeSH Terms
Animals
CD11c Antigen/metabolism
Carcinoma, Lewis Lung/pathology
Cell Movement
Dendritic Cells/physiology
Dermatitis, Contact/etiology,immunology
Glycoproteins/genetics,physiology
Hyaluronic Acid/blood,metabolism
Inflammation/chemically induced,immunology
Lymph Nodes/cytology,metabolism,physiology
Lymphatic Vessels/cytology,metabolism,physiology
Melanoma/pathology
Membrane Transport Proteins
Mice
Mice, Knockout
Neoplasm Transplantation
Oxazolone
beta-Galactosidase/genetics
Chemicals
CD11c Antigen
Glycoproteins
Membrane Transport Proteins
Xlkd1 protein, mouse
Oxazolone
Hyaluronic Acid
beta-Galactosidase
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Gale Nicholas W
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom.
Prevo Remko
Espinosa Jorge
Ferguson David J
Dominguez Melissa G
Yancopoulos George D
Thurston Gavin
Jackson David G
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