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Regulation of complement classical pathway by association of C4b-binding protein to the surfaces of SK-OV-3 and caov-3 ovarian adenocarcinoma cells

Holmberg, Mikko T.; Blom, Anna LU and Meri, Seppo (2001) In Journal of Immunology 167(2). p.935-939
Abstract
The role of fluid-phase regulators of complement is to inhibit excessive complement activation and maintain homeostasis in blood. By binding to and inactivating complement components on cell surfaces, they can also protect autologous cells from complement-mediated cytotoxicity and phagocytosis. In this study, we wanted to find out whether C4b-binding protein (C4bp), a fluid-phase regulator of the classical complement pathway, could directly bind to cell surfaces in a functionally active form. After screening several malignant cell lines, we observed that the ovarian adenocarcinoma cell lines SK-OV-3, Caov-3, and SW626 were capable of binding C4bp. Binding tests with recombinant deletion mutants suggested that the primary binding site on... (More)
The role of fluid-phase regulators of complement is to inhibit excessive complement activation and maintain homeostasis in blood. By binding to and inactivating complement components on cell surfaces, they can also protect autologous cells from complement-mediated cytotoxicity and phagocytosis. In this study, we wanted to find out whether C4b-binding protein (C4bp), a fluid-phase regulator of the classical complement pathway, could directly bind to cell surfaces in a functionally active form. After screening several malignant cell lines, we observed that the ovarian adenocarcinoma cell lines SK-OV-3, Caov-3, and SW626 were capable of binding C4bp. Binding tests with recombinant deletion mutants suggested that the primary binding site on C4bp is located on the alpha -chain complement control protein 4 domain. Functional tests showed that tumor cell-bound C4bp retained its cofactor activity for factor I-mediated inactivation of CO, thus increasing the control of classical complement pathway activation on the surfaces of these cells. These results demonstrate a novel mechanism of complement regulation on cell surfaces, particularly on those of malignant ovarian tumor cells. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
167
issue
2
pages
935 - 939
publisher
American Association of Immunologists
external identifiers
  • wos:000170949300041
  • scopus:0035879282
ISSN
1550-6606
language
English
LU publication?
yes
id
e91dbc85-71b5-4364-a5bb-351fcbe53783 (old id 1118943)
date added to LUP
2008-06-30 14:54:57
date last changed
2018-05-29 10:00:56
@article{e91dbc85-71b5-4364-a5bb-351fcbe53783,
  abstract     = {The role of fluid-phase regulators of complement is to inhibit excessive complement activation and maintain homeostasis in blood. By binding to and inactivating complement components on cell surfaces, they can also protect autologous cells from complement-mediated cytotoxicity and phagocytosis. In this study, we wanted to find out whether C4b-binding protein (C4bp), a fluid-phase regulator of the classical complement pathway, could directly bind to cell surfaces in a functionally active form. After screening several malignant cell lines, we observed that the ovarian adenocarcinoma cell lines SK-OV-3, Caov-3, and SW626 were capable of binding C4bp. Binding tests with recombinant deletion mutants suggested that the primary binding site on C4bp is located on the alpha -chain complement control protein 4 domain. Functional tests showed that tumor cell-bound C4bp retained its cofactor activity for factor I-mediated inactivation of CO, thus increasing the control of classical complement pathway activation on the surfaces of these cells. These results demonstrate a novel mechanism of complement regulation on cell surfaces, particularly on those of malignant ovarian tumor cells.},
  author       = {Holmberg, Mikko T. and Blom, Anna and Meri, Seppo},
  issn         = {1550-6606},
  language     = {eng},
  number       = {2},
  pages        = {935--939},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Regulation of complement classical pathway by association of C4b-binding protein to the surfaces of SK-OV-3 and caov-3 ovarian adenocarcinoma cells},
  volume       = {167},
  year         = {2001},
}