論文

査読有り
2014年6月

Direct cytocidal effect of galectin-9 localized on collagen matrices on human immune cell lines

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
  • Youko Fukata
  • ,
  • Aiko Itoh
  • ,
  • Yasuhiro Nonaka
  • ,
  • Takashi Ogawa
  • ,
  • Takanori Nakamura
  • ,
  • Osamu Matsushita
  • ,
  • Nozomu Nishi

1840
6
開始ページ
1892
終了ページ
1901
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbagen.2014.01.019
出版者・発行元
ELSEVIER SCIENCE BV

Background: There is a continuous demand for new immunosuppressive agents for organ transplantation. Galectin-9, a member of the galactoside-binding animal lectin family, has been shown to suppress pathogenic T-cell responses in autoimmune disease models and experimental allograft transplantation. In this study, an attempt has been made to develop new collagen matrices, which can cause local, contact-dependent immune suppression, using galectin-9 and collagen-binding galectin-9 fusion proteins as active ingredients.
Methods: Galectin-9 and galectin-9 fusion proteins having collagen-binding domains (CBDs) derived from bacterial collagenases and a collagen-binding peptide (CBP) were tested for their ability to bind to collagen matrices, and to induce Jurkat cell death in solution and in the collagen-bound state.
Results: Galectin-9-CBD fusion proteins exhibited collagen-binding activity comparable to or lower than that of the respective CBDs, while their cytocidal activity toward Jurkat cells in solution was 80 similar to 10% that of galectin-9. Galectin-9 itself exhibited oligosaccharide-dependent collagen-binding activity. The growth of Jurkat cells cultured on collagen membranes treated with galectin-9 was inhibited by -90%. The effect was dependent on direct cell-to-membrane contact. Galectin-9-CBD/CBP fusion proteins bound to collagen membranes via CBD/ CBP moieties showed a low or negligible effect on Jurlcat cell growth.
Conclusions: Among the proteins tested, galectin-9 exhibited the highest cytocidal effect on Jurkat cells in the collagen-bound state. The effect was not due to galectin-9 released into the culture medium but was dependent on direct cell-to-membrane contact.
General significance: The study demonstrates the possible use of galectin-9-modified collagen matrices for local, contact-dependent immune suppression in transplantation. (C) 2014 Elsevier B.V. All rights reserved.

リンク情報
DOI
https://doi.org/10.1016/j.bbagen.2014.01.019
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000336012700030&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.bbagen.2014.01.019
  • ISSN : 0304-4165
  • eISSN : 1872-8006
  • Web of Science ID : WOS:000336012700030

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