[HTML][HTML] Dissociation between mature phenotype and impaired transmigration in dendritic cells from heparanase-deficient mice

S Benhamron, I Reiner, E Zcharia, M Atallah, A Grau… - PloS one, 2012 - journals.plos.org
S Benhamron, I Reiner, E Zcharia, M Atallah, A Grau, I Vlodavsky, D Mevorach
PloS one, 2012journals.plos.org
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 …
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.
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