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

Youko Fukata, Aiko Itoh, Yasuhiro Nonaka, Takashi Ogawa, Takanori Nakamura, Osamu Matsushita, Nozomu Nishi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 ~ 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 Jurkat 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.

Original languageEnglish
Pages (from-to)1892-1901
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1840
Issue number6
DOIs
Publication statusPublished - Jun 2014

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Direct cytocidal effect of galectin-9 localized on collagen matrices on human immune cell lines'. Together they form a unique fingerprint.

  • Cite this