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.

CONCLUSION:

These findings reveal a novel function of heparanase in maintaining MC homeostasis through controlled degradation of heparin present in the MC secretory granules.

• Authors: Bo Wang, Juan Jia, Xiao Zhang, Eyal Zcharia, Israel Vlodavsky, Gunnar Pejler, Jin-Ping Li
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 128 Issue 6 Pg. 1310-1317.e8 (Dec 2011) ISSN: 1097-6825 [Electronic] United States
• PMID: 21575986 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Heparin
• heparanase
• Glucuronidase

Topics

• Animals
• Blotting, Western
• Cell Degranulation (immunology)
• Cells, Cultured
• Glucuronidase (immunology, metabolism)
• Heparin (immunology, metabolism)
• Homeostasis (immunology)
• Mast Cells (immunology, metabolism)
• Mice
• Mice, Knockout
• Mice, Transgenic
• Polymerase Chain Reaction
• Secretory Vesicles (immunology, metabolism)