MECHANISM OF REGULATING MOBILIZATION AND MIGRATION OF ANTIGEN PRESENTING CELLS DURING INFLAMMATION

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570507
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: NAGATA Hiroshi KEIO UNIVERSITY, MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (00146599)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Hidekazu KEIO UNIVERSITY, MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (70255454) ; SUEMATSU Makoto KEIO UNIVERSITY, MEDICINE, PROFESSOR, 医学部, 教授 (00206385) ; MINAMITANI Haruyuki KEIO UNIVERSITY, SCIENCE AND TECHNOLOGY, PROFESSOR, 医学部, 教授 (70051779)
• Project Period (FY): 2002 – 2004
• Keywords: macrophage / dendritic cell / colitis / lymphatic vessel in mesentery / mesenteric lymph node / chemokine

Research Abstract

Regulation of lymphocyte migration in the intestine under physiological and pathological condition
TECK/CCL25 plays an important role in the adherence of mucosal lymphocytes to the small intestine but not the colon under uniflamed as well as inflamed conditions. CD4T lymphocytes significantly accumulated in villus as well as in Peyer' s patches via a MAdCAM-1-dependent process in rats with a chronic allergy to ovalbumin.
Migration kinetics of dendritic cells via intestinal lymph
The isolated dendritic cells accumulated in mesenteric lymph nodes in a time-dependent manner with maximal accumulation at 48 h. Inhibition of ICAM-1 or CD11b/c did not affect DC migration. The migratory ability of dendritic cells correlates well with their degree of maturation, and different chemokine/chemokine receptor usage may be the main regulator of dendritic cell migration kinetics through intestinal lymph.
Response of macrophage in mesenteric lymph node
Parasinus macrophages play a role in the transient anti-metastatic capability of the node, and cytokines secreted by these cells increased at the early stages of metastasis. Deterioration of cytokine induction may be responsible for subsequent cancer proliferation. Macrophage migration inhibitory factor expressed in the cancer cells may modulate cytokine responses and migration of the macrophages.

Research Products

• [Journal Article] Limited capability of regional lymph nodes to eradicate metastatic cancer cells. (2004)
  • Author(s): Nagata H, Arai T, Soejima Y, Suzuki H, Ishii H, Hibi T.
  • Journal Title: Cancer Res 64 Pages: 8239-8248
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Chronic allergy to dietary ovalbumin induces lymphocyte migiration to rat small intestinal mucosa that is inhibited by MAdCAM-1. (2004)
  • Author(s): Ogawa T, Miura S, Tsuzuki Y, Nagata H, et al.
  • Journal Title: Am J Physiol (Gastrointest Liver Physiol) 286 Pages: G702-G710
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes : relationships to maturation and role of chemokines. (2004)
  • Author(s): Kobayashi H, Miura S, Nagata H, et al.
  • Journal Title: J Leukocyte Biol 75 Pages: 434-442
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Demonstration of functional role of TECK/CCL25 in Tlymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa. (2004)
  • Author(s): Hosoe N, Miura S, Watanabe C, Nagata H, et al.
  • Journal Title: Am J Physiol (Gastrointest Liver Physio) 286 Pages: G458-G466
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Chronic allergy to dietary ovalbumin induces lymphocyte migration to rat small intestinal mucosa that is inhibited by MAdCAM-1. (2004)
  • Author(s): Ogawa T, Miura S, Tsuzuki Y, Ogino T, Teramoto K, Inamura T, Watanabe C, Hokari R, Nagata H, Ishii H.
  • Journal Title: Am J Physiol (Gastrointest Liver Physiol 286) Pages: G702-G710
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes : relationships to maturation and role of chemokines. (2004)
  • Author(s): Kobayashi H, Miura S, Nagata H, Tsuzuki Y, Hokari R, Ogino T, Watanabe C, Azuma T, Ishii H.
  • Journal Title: J Leukocyte Biol 75 Pages: 434-442
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa. (2004)
  • Author(s): Hosoe N, Miura 5, Watanabe C, Tsuzuki Y, Hokari R, Oyama T, Fujiyama Y, Nagata H, Isahii H.
  • Journal Title: Am J Physiol(Gastrointest Liver Physiol 286) Pages: G458-G466
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alteration of intestinal intraepithelial lymphocytes and increased bacterial translocation in a murine model of cirrhosis. (2003)
  • Author(s): Inamura T, Miura S, Tsuzuki Y, Nagata H. et al.
  • Journal Title: Immunol Lett 90 Pages: 3-11
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Exposure to fatty acids modulates interferon production by intraepithelial lymphocytes. (2003)
  • Author(s): Hara Y, Miura S, Komoto S, Nagata H, et al.
  • Journal Title: Immunol Lett 86:139-148,2003. 86 Pages: 139-148
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alteration of intestinal intraepithelial lymphocytes and increased bacterial translocation in a murine model of cirrhosis. (2003)
  • Author(s): Inamura T, Miura S, Tsuzuki Y, Hara Y, Hokari R, Ogawa T, Teramoto K, Watanabe C, Kobayashi H, Nagata H, Ishii H.
  • Journal Title: Immunol Lett 90 Pages: 3-11
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Exposure to fatty acids modulates interferon production by intraepithelial lymphocytes. (2003)
  • Author(s): Hara Y, Miura S, Komoto S, Inamura T, Koseki S, Watanabe C, Hokari R, Tsuzuki Y, Ogino T, Nagata H, Hachimura S, Kaminogawa S, Ishii H.
  • Journal Title: Immunol Lett 86 Pages: 139-148
  • Description: 「研究成果報告書概要(欧文)」より