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Serglycin proteoglycan is required for secretory granule integrity in mucosal mast cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
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2007 (English)In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 403, no 1, 49-57 p.Article in journal (Refereed) Published
Abstract [en]

SG (serglycin) PGs (proteoglycans) are strongly implicated in the assembly of MC (mast cell) granules. However, this notion has mainly been on the basis of studies of MCs of the connective tissue subtype, whereas the role of SG PG in mucosal MCs has not been explored. In the present study, we have addressed the latter issue by using mice with an inactivated SG gene. Bone marrow cells were differentiated in vitro into the mucosal MC phenotype, expressing the markers mMCP (mouse MC protease) -1 and -2. Biosynthetic labelling experiments performed on these cells revealed an ~80% reduction of 35SO42− incorporation into PGs recovered from SG−/− cells as compared with SG+/+ counterparts, indicating that SG is the dominating cell-associated PG of mucosal MCs. Moreover, the absence of SG led to defective metachromatic staining of mucosal MCs, both in vivo and in the in vitro-derived mucosal MCs. Ultrastructural analysis showed that granules were present in similar numbers in SG+/+ and SG−/− cells, but that their morphology was markedly affected by the absence of SG, e.g. with electron-dense core formation only seen in SG+/+ granules. Analysis of the MC-specific proteases showed that mMCP-1 and mMCP-7 were completely independent of SG for storage, whereas mMCP-2 showed a partial dependence. In contrast, mMCP-4 and -6, and carboxypeptidase A were strongly dependent on SG for storage. Together, our data indicate that SG PG is of crucial importance for assembly of mature mucosal MC granules, but that the specific dependence on SG for storage varies between individual granule constituents.

Place, publisher, year, edition, pages
2007. Vol. 403, no 1, 49-57 p.
Keyword [en]
chymase, mast cell, protease, proteoglycan, serglycin, tryptase
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-10711DOI: 10.1042/BJ20061257ISI: 000245488400006PubMedID: 17147513OAI: oai:DiVA.org:uu-10711DiVA: diva2:38479
Available from: 2007-04-20 Created: 2007-04-20 Last updated: 2011-04-07Bibliographically approved

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Lukinius, AgnetaHellman, LarsÅbrink, Magnus
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Department of Genetics and PathologyDepartment of Cell and Molecular BiologyDepartment of Medical Biochemistry and Microbiology
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