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.
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.
Duelli
Annette
A
Department of Anatomy, Swedish University of Agricultural Sciences, Uppsala 75123, Sweden.
Rönnberg
Elin
E
Waern
Ida
I
Ringvall
Maria
M
Kolset
Svein O
SO
Pejler
Gunnar
G
D000581:Amidohydrolases / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002809:Chondroitin Sulfates / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D006493:Heparin / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015238:Sulfotransferases / Q000096:biosynthesis* / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000096:biosynthesis* / Q000235:genetics
D011509:Proteoglycans; D033921:Vesicular Transport Proteins; C075430:serglycin; D006493:Heparin; D002809:Chondroitin Sulfates; C491855:Ndst2 protein, mouse; D015238:Sulfotransferases; C021350:heparitin sulfotransferase; D000581:Amidohydrolases