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
| Autor: | Ida Waern, Svein Olav Kolset, Gunnar Pejler, Elin Rönnberg, Maria Ringvall, Annette Duelli |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Mast cell differentiation
Immunology Vesicular Transport Proteins Gene Expression Cytoplasmic Granules Amidohydrolases Mice chemistry.chemical_compound Sulfation medicine Animals Immunology and Allergy Serglycin Chondroitin Mast Cells Chondroitin sulfate biology Heparin Reverse Transcriptase Polymerase Chain Reaction Chemistry Chondroitin Sulfates Cell Differentiation Mast cell Mice Inbred C57BL medicine.anatomical_structure Gene Expression Regulation Proteoglycan Biochemistry biology.protein Proteoglycans Sulfotransferases medicine.drug |
| Zdroj: | The Journal of Immunology. 183:7073-7083 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0900309 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|