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*Departments of Anatomy, Physiology, and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden; and
Department of Nutrition, University of Oslo, Oslo, Norway
Serglycin (SG) proteoglycan consists of a small core protein to which glycosaminoglycans of chondroitin sulfate or heparin type are attached. SG is crucial for maintaining mast cell (MC) granule homeostasis through promoting the storage of various basic granule constituents, where the degree of chondroitin sulfate/heparin sulfation is essential for optimal SG functionality. However, the regulation of the SG core protein expression and of the various chondroitin sulfate/heparin sulfotransferases during MC differentiation and activation are poorly understood. Here we addressed these issues and show that expression of the SG core protein, chondroitin 4-sulfotransferase (C4ST)-1, and GalNAc(4S)-6-O-sulfotransferase (GalNAc4S6ST) are closely linked to MC maturation. In contrast, the expression of chondroitin 6-sulfotransferase correlated negatively with MC maturation. The expression of N-deacetylase/N-sulfotransferase (NDST)-2, a key enzyme in heparin synthesis, also correlated strongly with MC maturation, whereas the expression of the NDST-1 isoform was approximately equal at all stages of maturation. MC activation by either calcium ionophore or IgE ligation caused an up-regulated expression of the SG core protein, C4ST-1, and GalNAc4S6ST, accompanied by increased secretion of chondroitin sulfate as shown by biosynthetic labeling experiments. In contrast, NDST-2 was down-regulated after MC activation, suggesting that MC activation modulates the nature of the glycosaminoglycan chains attached to the SG core protein. Taken together, these data show that MC maturation is associated with the expression of a distinct signature of genes involved in SG proteoglycan synthesis, and that MC activation modulates their expression.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Swedish Research Council, the Swedish Cancer Foundation, Formas, and Gustaf V’s 80-Year Anniversary Foundation, and the Throne Holst Foundation.
2 A.D. and E.R. contributed equally to this work.
3 Current address: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
4 Address correspondence and reprint requests to Dr. Gunnar Pejler, Department of Anatomy, Physiology, and Biochemistry, Swedish University of Agricultural Sciences, BMC, Box 575, 75123 Uppsala, Sweden. E-mail address: Gunnar.Pejler{at}afb.slu.se
5 Abbreviations used in this paper: MC, mast cell; BMMC, bone marrow-derived mast cell; SG, serglycin; GAG, glycosaminoglycan; CS, chondroitin sulfate; GlcUA, glucuronic acid; IdoUA, iduronic acid; GlcNAc, N-acetyl-glucosamine; C4ST, chondroitin 4-sulfotransferase; GalNAc4S6ST, GalNAc(4S)-6-O-sulfotransferase; C6ST, chondroitin 6-sulfotransferase; HS, heparan sulfate; CTMC, connective tissue MC; SCF, stem cell factor; MMC, mucosal MC; PCMC, peritoneal MC; mMCP, mouse MC protease; NDST, N-deacetylase/N-sulfotransferase.
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