title: Heparanase affects secretory granule homeostasis of murine mast cells through degrading heparin.
abstract: BACKGROUND
  Heparanase degradation of heparan sulfate plays important roles in a number of pathological processes, including inflammation. In vitro experiments show that heparanase is capable of degrading heparin, a polysaccharide present in mast cells (MCs), in which it has a key role in promoting the storage of secretory granule compounds.
  
  
  OBJECTIVE
  We sought to investigate the functions of heparanase in MCs.
  
  
  METHODS
  Primarily cultured fetal skin-derived mast cells (FSMCs) isolated from embryos and adult peritoneal MCs were analyzed for storage and release of granule molecules in response to MC activation.
  
  
  RESULTS
  FSMCs from heparanase-overexpressing mice contained substantially shorter heparin chains and significantly less proteases than control cells. Conversely, FSMCs lacking heparanase contained heparin of larger size and more proteases than control cells. Correspondingly, heparanase-overexpressing adult MCs exhibited reduced release of heparin-bound proteases, a finding that could be attributed to spontaneous release of granular compounds. Heparanase was found to be upregulated in MCs on activation.
  
  
  CONCLUSIONS
  These findings reveal a novel function of heparanase in maintaining MC homeostasis through controlled degradation of heparin present in the MC secretory granules.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Jia
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Eyal
authors.initials: E
authors.lastname: Zcharia
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D005966:Glucuronidase / Q000276:immunology / Q000378:metabolism*; D006493:Heparin / Q000276:immunology / Q000378:metabolism*; D006706:Homeostasis / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D022142:Secretory Vesicles / Q000276:immunology / Q000378:metabolism*; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006493:Heparin; D000099175:Heparanase