Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis

Takanori Kanai, Koji Uraushihara, Teruji Totsuka, Yasuhiro Nemoto, Rei Fujii, Takahiro Kawamura, Shin Makita, Daisuke Sawada, Hideo Yagita, Ko Okumura, Mamoru Watanabe

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Crohn's disease (CD) is an inflammatory bowel disease that is associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) which are critically involved in the onset and the development of CD. The present study was performed to explore the initial involvement of macrophages in the development of T-cell-mediated chronic colitis. Methods: The effects were evaluated of saporin-conjugated anti-CD11b monoclonal antibody (mAb) on the development of chronic colitis in severe combined immunodeficiency (SCID) mice induced by adoptive transfer of CD4+CD45RBhigh T cells as an animal model of CD. Results: Significantly increased CD11b-expressing macrophages as well as CD4+ T cells were found in inflamed colon from colitic mice. Administration of saporin-conjugated anti-CD11b mAb markedly ameliorated the clinical and histopathological disease. In vivo treatment with saporin-conjugated anti-CD11b mAb decreased CD4+ T-cell infiltration in the colon and suppressed inferferon-γ (IFN-γ) and TNF-α production by lamina propria CD4+ T cells. Conclusions: Collectively, the present results suggest an initial role of macrophages in the pathogenesis of T-cell-mediated chronic colitis. Furthermore, the macrophage-specific targeting may be a promising strategy for therapeutic intervention in CD.

Original languageEnglish
Pages (from-to)1136-1142
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume21
Issue number7
DOIs
Publication statusPublished - 2006
Externally publishedYes

Fingerprint

Colitis
Macrophages
Monoclonal Antibodies
T-Lymphocytes
Crohn Disease
Colon
Tumor Necrosis Factor-alpha
Severe Combined Immunodeficiency
Adoptive Transfer
Inflammatory Bowel Diseases
saporin
Immune System
Mucous Membrane
Animal Models
Cytokines
Therapeutics

Keywords

  • Crohn's disease
  • Macrophages
  • Murine model
  • Targeting
  • Therapy

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis. / Kanai, Takanori; Uraushihara, Koji; Totsuka, Teruji; Nemoto, Yasuhiro; Fujii, Rei; Kawamura, Takahiro; Makita, Shin; Sawada, Daisuke; Yagita, Hideo; Okumura, Ko; Watanabe, Mamoru.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 21, No. 7, 2006, p. 1136-1142.

Research output: Contribution to journalArticle

Kanai, T, Uraushihara, K, Totsuka, T, Nemoto, Y, Fujii, R, Kawamura, T, Makita, S, Sawada, D, Yagita, H, Okumura, K & Watanabe, M 2006, 'Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis', Journal of Gastroenterology and Hepatology (Australia), vol. 21, no. 7, pp. 1136-1142. https://doi.org/10.1111/j.1440-1746.2006.04391.x
Kanai, Takanori ; Uraushihara, Koji ; Totsuka, Teruji ; Nemoto, Yasuhiro ; Fujii, Rei ; Kawamura, Takahiro ; Makita, Shin ; Sawada, Daisuke ; Yagita, Hideo ; Okumura, Ko ; Watanabe, Mamoru. / Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis. In: Journal of Gastroenterology and Hepatology (Australia). 2006 ; Vol. 21, No. 7. pp. 1136-1142.
@article{99fc92216d70446bba0d312298fd9859,
title = "Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis",
abstract = "Background: Crohn's disease (CD) is an inflammatory bowel disease that is associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) which are critically involved in the onset and the development of CD. The present study was performed to explore the initial involvement of macrophages in the development of T-cell-mediated chronic colitis. Methods: The effects were evaluated of saporin-conjugated anti-CD11b monoclonal antibody (mAb) on the development of chronic colitis in severe combined immunodeficiency (SCID) mice induced by adoptive transfer of CD4+CD45RBhigh T cells as an animal model of CD. Results: Significantly increased CD11b-expressing macrophages as well as CD4+ T cells were found in inflamed colon from colitic mice. Administration of saporin-conjugated anti-CD11b mAb markedly ameliorated the clinical and histopathological disease. In vivo treatment with saporin-conjugated anti-CD11b mAb decreased CD4+ T-cell infiltration in the colon and suppressed inferferon-γ (IFN-γ) and TNF-α production by lamina propria CD4+ T cells. Conclusions: Collectively, the present results suggest an initial role of macrophages in the pathogenesis of T-cell-mediated chronic colitis. Furthermore, the macrophage-specific targeting may be a promising strategy for therapeutic intervention in CD.",
keywords = "Crohn's disease, Macrophages, Murine model, Targeting, Therapy",
author = "Takanori Kanai and Koji Uraushihara and Teruji Totsuka and Yasuhiro Nemoto and Rei Fujii and Takahiro Kawamura and Shin Makita and Daisuke Sawada and Hideo Yagita and Ko Okumura and Mamoru Watanabe",
year = "2006",
doi = "10.1111/j.1440-1746.2006.04391.x",
language = "English",
volume = "21",
pages = "1136--1142",
journal = "Journal of Gastroenterology and Hepatology (Australia)",
issn = "0815-9319",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis

AU - Kanai, Takanori

AU - Uraushihara, Koji

AU - Totsuka, Teruji

AU - Nemoto, Yasuhiro

AU - Fujii, Rei

AU - Kawamura, Takahiro

AU - Makita, Shin

AU - Sawada, Daisuke

AU - Yagita, Hideo

AU - Okumura, Ko

AU - Watanabe, Mamoru

PY - 2006

Y1 - 2006

N2 - Background: Crohn's disease (CD) is an inflammatory bowel disease that is associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) which are critically involved in the onset and the development of CD. The present study was performed to explore the initial involvement of macrophages in the development of T-cell-mediated chronic colitis. Methods: The effects were evaluated of saporin-conjugated anti-CD11b monoclonal antibody (mAb) on the development of chronic colitis in severe combined immunodeficiency (SCID) mice induced by adoptive transfer of CD4+CD45RBhigh T cells as an animal model of CD. Results: Significantly increased CD11b-expressing macrophages as well as CD4+ T cells were found in inflamed colon from colitic mice. Administration of saporin-conjugated anti-CD11b mAb markedly ameliorated the clinical and histopathological disease. In vivo treatment with saporin-conjugated anti-CD11b mAb decreased CD4+ T-cell infiltration in the colon and suppressed inferferon-γ (IFN-γ) and TNF-α production by lamina propria CD4+ T cells. Conclusions: Collectively, the present results suggest an initial role of macrophages in the pathogenesis of T-cell-mediated chronic colitis. Furthermore, the macrophage-specific targeting may be a promising strategy for therapeutic intervention in CD.

AB - Background: Crohn's disease (CD) is an inflammatory bowel disease that is associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) which are critically involved in the onset and the development of CD. The present study was performed to explore the initial involvement of macrophages in the development of T-cell-mediated chronic colitis. Methods: The effects were evaluated of saporin-conjugated anti-CD11b monoclonal antibody (mAb) on the development of chronic colitis in severe combined immunodeficiency (SCID) mice induced by adoptive transfer of CD4+CD45RBhigh T cells as an animal model of CD. Results: Significantly increased CD11b-expressing macrophages as well as CD4+ T cells were found in inflamed colon from colitic mice. Administration of saporin-conjugated anti-CD11b mAb markedly ameliorated the clinical and histopathological disease. In vivo treatment with saporin-conjugated anti-CD11b mAb decreased CD4+ T-cell infiltration in the colon and suppressed inferferon-γ (IFN-γ) and TNF-α production by lamina propria CD4+ T cells. Conclusions: Collectively, the present results suggest an initial role of macrophages in the pathogenesis of T-cell-mediated chronic colitis. Furthermore, the macrophage-specific targeting may be a promising strategy for therapeutic intervention in CD.

KW - Crohn's disease

KW - Macrophages

KW - Murine model

KW - Targeting

KW - Therapy

UR - http://www.scopus.com/inward/record.url?scp=33745202616&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745202616&partnerID=8YFLogxK

U2 - 10.1111/j.1440-1746.2006.04391.x

DO - 10.1111/j.1440-1746.2006.04391.x

M3 - Article

C2 - 16824065

AN - SCOPUS:33745202616

VL - 21

SP - 1136

EP - 1142

JO - Journal of Gastroenterology and Hepatology (Australia)

JF - Journal of Gastroenterology and Hepatology (Australia)

SN - 0815-9319

IS - 7

ER -