title: Dissociation between mature phenotype and impaired transmigration in dendritic cells from heparanase-deficient mice.
abstract: To reach the lymphatics, migrating dendritic cells (DCs) need to interact with the extracellular matrix (ECM). Heparanase, a mammalian endo-β-D-glucuronidase, specifically degrades heparan sulfate proteoglycans ubiquitously associated with the cell surface and ECM. The role of heparanase in the physiology of bone marrow-derived DCs was studied in mutant heparanase knock-out (Hpse-KO) mice. Immature DCs from Hpse-KO mice exhibited a more mature phenotype; however their transmigration was significantly delayed, but not completely abolished, most probably due to the observed upregulation of MMP-14 and CCR7. Despite their mature phenotype, uptake of beads was comparable and uptake of apoptotic cells was more efficient in DCs from Hpse-KO mice. Heparanase is an important enzyme for DC transmigration. Together with CCR7 and its ligands, and probably MMP-14, heparanase controls DC trafficking.
authors.affiliation: The Laboratory for Cellular and Molecular Immunology, Department of Medicine, Rheumatology Research Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Benhamron
authors.forename: Inna
authors.initials: I
authors.lastname: Reiner
authors.forename: Eyal
authors.initials: E
authors.lastname: Zcharia
authors.forename: Mizhir
authors.initials: M
authors.lastname: Atallah
authors.forename: Amir
authors.initials: A
authors.lastname: Grau
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: Dror
authors.initials: D
authors.lastname: Mevorach
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D005109:Extracellular Matrix / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006497:Heparan Sulfate / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006497:Heparan Sulfate; D053511:Matrix Metalloproteinase 14; D054400:Receptors, CCR7; D000099175:Heparanase; C515371:Ccr7 protein, mouse; C507096:Mmp14 protein, mouse