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 - 2014

Fingerprint

Galectins
Collagen
Cells
Cell Line
Jurkat Cells
Fusion reactions
Membranes
Proteins
Peptides
Transplantation
Cell Membrane
Transplantation (surgical)
Galactosides

Keywords

  • Collagen
  • Collagen-binding domain
  • Galectin
  • Immune suppression

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Direct cytocidal effect of galectin-9 localized on collagen matrices on human immune cell lines. / Fukata, Youko; Itoh, Aiko; Nonaka, Yasuhiro; Ogawa, Takashi; Nakamura, Takanori; Matsushita, Osamu; Nishi, Nozomu.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1840, No. 6, 2014, p. 1892-1901.

Research output: Contribution to journalArticle

Fukata, Youko ; Itoh, Aiko ; Nonaka, Yasuhiro ; Ogawa, Takashi ; Nakamura, Takanori ; Matsushita, Osamu ; Nishi, Nozomu. / Direct cytocidal effect of galectin-9 localized on collagen matrices on human immune cell lines. In: Biochimica et Biophysica Acta - General Subjects. 2014 ; Vol. 1840, No. 6. pp. 1892-1901.
@article{3cf177c1248848b0b76c9e685d5d2821,
title = "Direct cytocidal effect of galectin-9 localized on collagen matrices on human immune cell lines",
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.",
keywords = "Collagen, Collagen-binding domain, Galectin, Immune suppression",
author = "Youko Fukata and Aiko Itoh and Yasuhiro Nonaka and Takashi Ogawa and Takanori Nakamura and Osamu Matsushita and Nozomu Nishi",
year = "2014",
doi = "10.1016/j.bbagen.2014.01.019",
language = "English",
volume = "1840",
pages = "1892--1901",
journal = "Biochimica et Biophysica Acta - General Subjects",
issn = "0304-4165",
publisher = "Elsevier",
number = "6",

}

TY - JOUR

T1 - Direct cytocidal effect of galectin-9 localized on collagen matrices on human immune cell lines

AU - Fukata, Youko

AU - Itoh, Aiko

AU - Nonaka, Yasuhiro

AU - Ogawa, Takashi

AU - Nakamura, Takanori

AU - Matsushita, Osamu

AU - Nishi, Nozomu

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Collagen

KW - Collagen-binding domain

KW - Galectin

KW - Immune suppression

UR - http://www.scopus.com/inward/record.url?scp=84897099799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897099799&partnerID=8YFLogxK

U2 - 10.1016/j.bbagen.2014.01.019

DO - 10.1016/j.bbagen.2014.01.019

M3 - Article

C2 - 24462947

AN - SCOPUS:84897099799

VL - 1840

SP - 1892

EP - 1901

JO - Biochimica et Biophysica Acta - General Subjects

JF - Biochimica et Biophysica Acta - General Subjects

SN - 0304-4165

IS - 6

ER -