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Unveiling the biological role of serglycin proteoglycans

studies on serglycin knock-out mice

Braga M. C. Carlos, Tiago (2008). Unveiling the biological role of serglycin proteoglycans. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2008:14
ISBN 978-91-85913-47-3
[Doctoral thesis]

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Abstract

Serglycin (SG) proteoglycans (PG) are predominantly located intracellularly in secretory vesicles of hematopoietic cells such as macrophages, cytotoxic T lymphocytes (CTLs), monocytes, basophils, neutrophils and mast cells (MCs). These PGs are characterized by their protease-resistant serine and glycine-rich core and also by their covalently attached negatively charged glycosaminoglycans (GAG) chains. We showed that SG PGs are the dominant PGs species in CTLs where they contributed to proper sub-structural organization of the secretory vesicles. Furthermore, different granule-specific components exhibited distinct SG PG dependence for storage, where granzyme B levels were shown to be highly affected, while granzyme A or perforin levels were not. MCs are important immune cells that release preformed mediators upon activation. We confirmed that SG PGs are the major PG species in mucosal-like bone marrow-derived MCs (BMMCs) and their absence leads to defects in the granule organization and inability to store specific granule components (mMCP-5, CPA). However, mMCP-1 and mMCP-7 are not dependent on SG for storage. SG-dependent granule compounds exert many functions in homeostasis and interactions between immune cells. We noted that older SG-/- animals spontaneously developed enlarged peripheral lymphoid organs, namely the spleen and Peyer’s patches. Additionally, investigations of the spleen cell population from SG-/- revealed an increased population of CD45RC expressing cells but a reduction in CD4 positive cells. Sorting of SG PGs into secretory vesicles is a poorly understood process. We showed that in the presence of a reducing agent, granules in SG+/+ BMMCs show a striking resemblance to those found in SG-/- cells lacking a defined granular organization. Moreover, CPA’s storage was shown to be affected by the presence of the reducing agent, possibly due to its interaction with intra-granular SG PGs.

Authors/Creators:Braga M. C. Carlos, Tiago
Title:Unveiling the biological role of serglycin proteoglycans
Subtitle:studies on serglycin knock-out mice
Year of publishing :2008
Volume:2008:14
Number of Pages:62
Papers/manuscripts:
NumberReferences
ALLI. Grujic M., Braga T., Lukinius A., Eloranta, ML., Knight, SD., Pejler, G., Abrink, M., (2005). Serglycin-deficient cytotoxic T lymphocytes display defective secretory granule maturation and granzyme B storage. Journal of Biological Chemistry 280(39), 33411-8. II. Braga, T., Grujic, M., Lukinius, A., Hellman, L., Abrink, M., Pejler, G., (2007). Serglycin proteoglycan is required for secretory granule integrity in mucosal mast cells. Biochemical Journal 403(1), 49 -57. III. Wernersson, S., Braga, T., Sawesi, O., Nilsson, K., Pejler, G., Abrink, M., Age-related enlargement of lymphoid tissue and altered leukocyte composition in serglycin-deficient mice. Manuscript. IV. Braga T., Ringvall, M., Tveit, H., Abrink, M., Pejler, G., Reduction with Dithiothreitol Causes Serglycin-Specific Defects in Secretory Granule Integrity of Bone Marrow Derived Mast Cells. Manuscript
Place of Publication:Uppsala
ISBN for printed version:978-91-85913-47-3
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agrovoc terms:proteoglycans, glycosaminoglycans, mice, mast cells, toxicity, immunology, inflammation
Keywords:serglycin, hematopoietic cells, secretory granules, mast cells, cytotoxic T lymphocytes, immune system, inflammation
URN:NBN:urn:nbn:se:slu:epsilon-2542
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-2542
ID Code:1833
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
Deposited By: Tiago Braga
Deposited On:30 Sep 2008 00:00
Metadata Last Modified:02 Dec 2014 10:14

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