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Serglycin inhibits the classical and lectin pathways of complement via its glycosaminoglycan chains: Implications for multiple myeloma

Skliris, Antonis; Happonen, Kaisa LU ; Terpos, Evangelos; Labropoulou, Vassiliki; Borset, Magne; Heinegård, Dick LU ; Blom, Anna LU and Theocharis, Achilleas D. (2011) In European Journal of Immunology 41(2). p.437-449
Abstract
Serglycin (SG) is a proteoglycan expressed by hematopoietic cells and is constitutively secreted by multiple myeloma (MM) cells. SG participates in the regulation of various inflammatory events. We found that SG secreted by human MM cell lines inhibits both the classical and lectin pathways of complement, without influencing alternative pathway activity. The inhibitory effect of SG is due to direct interactions with C1q and mannose-binding lectin (MBL). C1q-binding is mediated through the glycosaminoglycan moieties of SG, whereas MBL binds additionally to SG protein core. Interactions between SG and C1q as well as MBL are diminished in the presence of chondroitin sulfate type E. In addition, we localized the SG-binding site to the... (More)
Serglycin (SG) is a proteoglycan expressed by hematopoietic cells and is constitutively secreted by multiple myeloma (MM) cells. SG participates in the regulation of various inflammatory events. We found that SG secreted by human MM cell lines inhibits both the classical and lectin pathways of complement, without influencing alternative pathway activity. The inhibitory effect of SG is due to direct interactions with C1q and mannose-binding lectin (MBL). C1q-binding is mediated through the glycosaminoglycan moieties of SG, whereas MBL binds additionally to SG protein core. Interactions between SG and C1q as well as MBL are diminished in the presence of chondroitin sulfate type E. In addition, we localized the SG-binding site to the collagen-like stalk of C1q. Interactions between SG and C1q as well as MBL are ionic in character and only the interaction with MBL was found to be partially dependent on the presence of calcium. We found the serum levels of SG to be elevated in patients with MM compared to healthy controls. Moreover, we found that SG expressed from myeloma plasma cells protects these cells from complement activation induced by treatment with anti-thymocyte immunoglobulins. This might protect myeloma cells during immunotherapy and promote survival of malignant cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Complement, Multiple myeloma, Serglycin
in
European Journal of Immunology
volume
41
issue
2
pages
437 - 449
publisher
John Wiley & Sons
external identifiers
  • wos:000287159600020
  • scopus:78851470656
ISSN
1521-4141
DOI
10.1002/eji.201040429
language
English
LU publication?
yes
id
0e2e56ec-fb31-4f32-a7a7-95d1b53c662b (old id 1882591)
date added to LUP
2011-04-01 08:40:00
date last changed
2017-10-08 03:11:52
@article{0e2e56ec-fb31-4f32-a7a7-95d1b53c662b,
  abstract     = {Serglycin (SG) is a proteoglycan expressed by hematopoietic cells and is constitutively secreted by multiple myeloma (MM) cells. SG participates in the regulation of various inflammatory events. We found that SG secreted by human MM cell lines inhibits both the classical and lectin pathways of complement, without influencing alternative pathway activity. The inhibitory effect of SG is due to direct interactions with C1q and mannose-binding lectin (MBL). C1q-binding is mediated through the glycosaminoglycan moieties of SG, whereas MBL binds additionally to SG protein core. Interactions between SG and C1q as well as MBL are diminished in the presence of chondroitin sulfate type E. In addition, we localized the SG-binding site to the collagen-like stalk of C1q. Interactions between SG and C1q as well as MBL are ionic in character and only the interaction with MBL was found to be partially dependent on the presence of calcium. We found the serum levels of SG to be elevated in patients with MM compared to healthy controls. Moreover, we found that SG expressed from myeloma plasma cells protects these cells from complement activation induced by treatment with anti-thymocyte immunoglobulins. This might protect myeloma cells during immunotherapy and promote survival of malignant cells.},
  author       = {Skliris, Antonis and Happonen, Kaisa and Terpos, Evangelos and Labropoulou, Vassiliki and Borset, Magne and Heinegård, Dick and Blom, Anna and Theocharis, Achilleas D.},
  issn         = {1521-4141},
  keyword      = {Complement,Multiple myeloma,Serglycin},
  language     = {eng},
  number       = {2},
  pages        = {437--449},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {Serglycin inhibits the classical and lectin pathways of complement via its glycosaminoglycan chains: Implications for multiple myeloma},
  url          = {http://dx.doi.org/10.1002/eji.201040429},
  volume       = {41},
  year         = {2011},
}