Mast Cell Differentiation and Activation Is Closely Linked to Expression of Genes Coding for the Serglycin Proteoglycan Core Protein and a Distinct Set of Chondroitin Sulfate and Heparin Sulfotransferases
Mast Cell Differentiation and Activation Is Closely Linked to Expression of Genes Coding for the Serglycin Proteoglycan Core Protein and a Distinct Set of Chondroitin Sulfate and Heparin Sulfotransferases
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DOI：
10.4049/jimmunol.0900309
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发表时间：
2009-12-01
影响因子：
4.4
通讯作者：
Pejler, Gunnar
中科院分区：
文献类型：
--
作者：
Duelli, Annette;Ronnberg, Elin;Pejler, Gunnar
丝甘肽（SG）蛋白聚糖由一个小的核心蛋白组成，硫酸软骨素或肝素型的糖胺聚糖附着在该核心蛋白上。SG通过促进各种基本颗粒成分的储存来维持肥大细胞（MC）颗粒稳态是至关重要的，其中硫酸软骨素/肝素硫酸化的程度对于最佳SG功能是必不可少的。然而，在MC分化和活化过程中，SG核心蛋白表达和各种硫酸软骨素/肝素磺基转移酶的调节知之甚少。在这里，我们解决了这些问题，并表明SG核心蛋白，软骨素4-磺基转移酶（C4 ST）-1，GaINAc（4S）-6-O-磺基转移酶（GaINAc 4S 6ST）的表达与MC成熟密切相关。相反，软骨素6-磺基转移酶的表达与MC成熟呈负相关。N-脱乙酰基酶/N-磺基转移酶（NDST）-2，在肝素合成的关键酶的表达，也与MC成熟强烈相关，而NDST-I亚型的表达是在所有阶段的成熟大致相等。通过钙离子载体或IgE连接的MC活化引起SG核心蛋白、C4 ST-1和GaINAc 4S 6ST的上调表达，伴随着硫酸软骨素分泌的增加，如生物合成标记实验所示。相比之下，NDST-2下调MC激活后，表明MC激活调节的性质的糖胺聚糖链连接到SG核心蛋白。两者合计，这些数据表明，MC成熟与SG蛋白聚糖合成中涉及的基因的不同签名的表达，MC激活调节其表达。免疫学杂志，2009，183：7073-7083.
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 GaINAc(4S)-6-O-sulfotransferase (GaINAc4S6ST) 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-I 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 GaINAc4S6ST, 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 Journal of Immunology, 2009, 183: 7073-7083.