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]
![]() |
PDF
569kB |
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 | ||||
Series Name/Journal: | Acta Universitatis Agriculturae Sueciae | ||||
Year of publishing : | 2008 | ||||
Number: | 2008:14 | ||||
Number of Pages: | 62 | ||||
Papers/manuscripts: |
| ||||
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 |
Repository Staff Only: item control page