Journal Article

Dissociation between Mature Phenotype and Impaired Transmigration in Dendritic Cells from Heparanase-Deficient Mice

Vlodavsky, Israel, Mevorach, Dror, Reiner, Inna, Zcharia, Eyal, Grau, Amir, Atallah, Mizhir, Benhamron, Sandrine

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Angiogenesis / Animals / Apoptosis / Beads / Biology / Bone marrow / Bone Marrow Cells - enzymology / Bone Marrow Cells - immunology / Cancer / CC chemokine receptors / CCR7 protein / Cell migration / Cell surface / Chemokines / Cloning / Dendritic cells / Dendritic Cells - enzymology / Dendritic Cells - immunology / Dissociation / Endothelium / Enzymes / Extracellular matrix / Extracellular Matrix - genetics / Extracellular Matrix - immunology / Extracellular Matrix - metabolism / Gene expression / Genetic aspects / Genotype & phenotype / Glucuronidase - genetics / Glucuronidase - immunology / Glucuronidase - metabolism / Heparan sulfate / Heparan sulfate proteoglycans / Heparitin Sulfate - genetics / Heparitin Sulfate - immunology / Heparitin Sulfate - metabolism / Immunology / Laboratories / Matrix Metalloproteinase 14 - biosynthesis / Matrix Metalloproteinase 14 - genetics / Matrix Metalloproteinase 14 - immunology / Medicine / Metastasis / Mice / Mice, Knockout / Morphology / Physiological aspects / Proteoglycans / Receptors, CCR7 - biosynthesis / Receptors, CCR7 - genetics / Receptors, CCR7 - immunology / Rheumatology / Rodents / Sulfate / Sulfates / Transendothelial and Transepithelial Migration - genetics / Transendothelial and Transepithelial Migration - immunology / Up-Regulation - genetics / Up-Regulation - immunology