Abstract
Serglycin is a proteoglycan composed of a relatively small (∼17 kDa) core protein to which sulfated glycosaminoglycans of either heparin, heparan sulfate or chondroitin sulfate types are attached. Serglycin is expressed in many cell types, including in particular cells of hematopoietic origin. To study the function of serglycin, we have used a serglycin knockout mouse strain. A striking finding was that the mast cell population was severely affected by the absence of serglycin, as evidenced by distorted granule morphology and defective staining with cationic dyes. Moreover, the absence of serglycin caused a dramatic effect on the ability of mast cells to store a number of granule compounds, including several mast cell-specific proteases as well as biogenic amines. Hence, serglycin has a major function in maintaining mast cell secretory granule homeostasis.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- MC:
-
Mast cell
- BMMC:
-
Bone marrow-derived mast cell
- mMCP:
-
Mouse mast cell protease
- CS:
-
Chondroitin sulfate
- PG:
-
Proteoglycan
- GAG:
-
Glycosaminoglycan
- SCF:
-
Stem cell factor
- MC-CPA:
-
Mast cell carboxypeptidase A
- HPRT:
-
Hypoxanthine guanine phosphoribosyl transferase
- NDST:
-
N-deacetylase/N-sulfotransferase
- GalNAc:
-
N-acetyl-galactosamine
- C4ST:
-
Chondroitin 4-sulfotransferase
- GalNAc4S6ST:
-
GalNAc(4S)-6-O-sulfotransferase
- C6ST:
-
Chondroitin 6-sulfotransferase
- GlcUA:
-
Glucuronic acid
- IdoUA:
-
Iduronic acid
- WT:
-
Wild type
References
Metcalfe, D. D., Baram, D., and Mekori, Y. A. (1997) Mast cells. Physiol Rev 77, 1033–1079.
Galli, S. J., Nakae, S., and Tsai, M. (2005) Mast cells in the development of adaptive immune responses. Nat Immunol. 6, 135–142.
Yu, M., Tsai, M., Tam, S. Y., Jones, C., Zehnder, J., and Galli, S. J. (2006) Mast cells can promote the development of multiple features of chronic asthma in mice. J Clin Invest. 116, 1633–1641.
Lee, D. M., Friend, D. S., Gurish, M. F., Benoist, C., Mathis, D., and Brenner, M. B. (2002) Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 297, 1689–1692.
Secor, V. H., Secor, W. E., Gutekunst, C. A., and Brown, M. A. (2000) Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis. J Exp Med. 191, 813–822.
Liu, J., Divoux, A., Sun, J., Zhang, J., Clement, K., Glickman, J. N., et al. (2009) Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med. 15, 940–945.
Sun, J., Sukhova, G. K., Yang, M., Wolters, P. J., MacFarlane, L. A., Libby, P., et al. (2007) Mast cells modulate the pathogenesis of elastase-induced abdominal aortic aneurysms in mice. J Clin Invest. 117, 3359–3368.
Sun, J., Sukhova, G. K., Wolters, P. J., Yang, M., Kitamoto, S., Libby, P., et al. (2007) Mast cells promote atherosclerosis by releasing proinflammatory cytokines. Nat Med. 13, 719–724.
Soucek, L., Lawlor, E. R., Soto, D., Shchors, K., Swigart, L. B., and Evan, G. I. (2007) Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat Med. 13, 1211–1218.
Malaviya, R., Ross, E. A., MacGregor, J. I., Ikeda, T., Little, J. R., Jakschik, B. A., and Abraham, S. N. (1994) Mast cell phagocytosis of FimH-expressing enterobacteria. J Immunol. 152, 1907–1914.
Echtenacher, B., Mannel, D. N., and Hultner, L. (1996) Critical protective role of mast cells in a model of acute septic peritonitis. Nature 381, 75–77.
Marshall, J. S. (2004) Mast-cell responses to pathogens. Nature reviews 4, 787–799.
Pejler, G., Åbrink, M., Ringvall, M., and Wernersson, S. (2007) Mast cell proteases. Adv Immunol. 95, 167–255.
Pejler, G., Abrink, M., and Wernersson, S. (2009) Serglycin proteoglycan: regulating the storage and activities of hematopoietic proteases. Biofactors 35, 61–68.
Kolset, S. O. and Tveit, H. (2008) Serglycin - Structure and biology. Cell Mol Life Sci. 65, 1073–1085.
Bishop, J. R., Schuksz, M., and Esko, J. D. (2007) Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature 446, 1030–1037.
Oldberg, A., Hayman, E. G., and Ruoslahti, E. (1981) Isolation of a chondroitin sulfate proteoglycan from a rat yolk sac tumor and immunochemical demonstration of its cell surface localization. J Biol Chem. 256, 10847–10852.
Bourdon, M. A., Oldberg, A., Pierschbacher, M., and Ruoslahti, E. (1985) Molecular cloning and sequence analysis of a chondroitin sulfate proteoglycan cDNA. Proc Natl Acad Sci USA 82, 1321–1325.
Kjellén, L., Pettersson, I., Lillhager, P., Steen, M. L., Pettersson, U., Lehtonen, P., et al. (1989) Primary structure of a mouse mastocytoma proteoglycan core protein. Biochem J. 263, 105–113.
Tantravahi, R. V., Stevens, R. L., Austen, K. F., and Weis, J. H. (1986) A single gene in mast cells encodes the core peptides of heparin and chondroitin sulfate proteoglycans. Proc Natl Acad Sci USA 83, 9207–9210.
Stevens, R. L., Fox, C. C., Lichtenstein, L. M., and Austen, K. F. (1988) Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells. Proc Natl Acad Sci USA 85, 2284–2287.
Åbrink, M., Grujic, M., and Pejler, G. (2004) Serglycin is essential for maturation of mast cell secretory granule. J Biol Chem. 279, 40897–40905.
Braga, T., Grujic, M., Lukinius, A., Hellman, L., Abrink, M., and Pejler, G. (2007) Serglycin proteoglycan is required for secretory granule integrity in mucosal mast cells. Biochem J. 403, 49–57.
Ringvall, M., Rönnberg, E., Wernersson, S., Duelli, A., Henningsson, F., Åbrink, M., et al. (2008) Serotonin and histamine storage in mast cell secretory granules is dependent on serglycin proteoglycan. J Allergy Clin Immunol. 121, 1020–1026.
Woulfe, D. S., Lilliendahl, J. K., August, S., Rauova, L., Kowalska, M. A., Abrink, M., et al. (2008) Serglycin proteoglycan deletion induces defects in platelet aggregation and thrombus formation in mice. Blood 111, 3458–3467.
Niemann, C. U., Abrink, M., Pejler, G., Fischer, R. L., Christensen, E. I., Knight, S. D., and Borregaard, N. (2007) Neutrophil elastase depends on serglycin proteoglycan for localization in granules. Blood 109, 4478–4486.
Grujic, M., Braga, T., Lukinius, A., Eloranta, M. L., Knight, S. D., Pejler, G., and Abrink, M. (2005) Serglycin-deficient cytotoxic T lymphocytes display defective secretory granule maturation and granzyme B storage. J Biol Chem. 280, 33411–33418.
Miller, H. R., Wright, S. H., Knight, P. A., and Thornton, E. M. (1999) A novel function for transforming growth factor-beta1: upregulation of the expression and the IgE-independent extracellular release of a mucosal mast cell granule-specific beta-chymase, mouse mast cell protease-1. Blood 93, 3473–3486.
Acknowledgments
The authors of this chapter receive support from The Swedish Research Council, Formas, King Gustaf V’s 80-year Anniversary Fund, Torsten and Ragnar Söderberg Foundation, and The Swedish Cancer Foundation.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Rönnberg, E., Pejler, G. (2012). Serglycin: The Master of the Mast Cell. In: Rédini, F. (eds) Proteoglycans. Methods in Molecular Biology, vol 836. Humana Press. https://doi.org/10.1007/978-1-61779-498-8_14
Download citation
DOI: https://doi.org/10.1007/978-1-61779-498-8_14
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-497-1
Online ISBN: 978-1-61779-498-8
eBook Packages: Springer Protocols