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Regulatory mechanism of antigen-stimulated lymphocyte migration in intestinal mucosa

Research Project

Project/Area Number 08457174
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKeio University

Principal Investigator

MIURA Soichiro  Keio University, Dept.of Medicine, Associate Professor, 医学部・内科, 助教授 (50138012)

Co-Investigator(Kenkyū-buntansha) SHIGEMATSU Takeharu  Keio University, Department of Medicine, 医学部・内科, 助手 (10245483)
SERIZAWA Hiroshi  Kitasato Institute Hospital, Department of Medicine, 付属病院・内科, 医員(研究職) (60187870)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥5,500,000 (Direct Cost: ¥5,500,000)
KeywordsPeyer's patch / Tlymphocyte migration / Postcapillary venule / Endotoxin / Concanavalin A / PG-PS / alpha4-integrin / intestinal inflammation / Tリンパ球homing / PG / PS / α4-integrin / postcapillary venule / リンパ球接着 / 腸粘膜 / Tリンパ球 / 抗原 / Con A(Concanavalin A) / 血管内皮 / リンパ球 migration
Research Abstract

Lymphocytes from gut associated lymphoid tissue (GALT) continuously recirculate throughout systemic circulation and play an important role for intestinal mucosal defense. In this study, we have established an observatory system of lymphocyte migration in rat Peyer's patches using intravital fluorescence microscopy and investigated the altered migration pattem of stimulated T cells as compared with naive T cells. Con A-stimulation of T cells showed the loss of selective adherent properties in Peyer's patches as shown in naive T cells. On the other hand, the adherence of T cells to hepatic sinusoidal endothelium was significantly increased after Con A activation. The enhanced rolling and adherence of lymphocytes was observed in Peyer's patches and submucosal venules of villi when rats were treated with endotoxin, and these changes were mediated largely by alpha4- integrins.Intestinal inflammation was also induced by an intramural injection of peptidoglycan-polysaccharide (PG-PS) from group A streptococci into rat ileal Peyer's patches. We also demonstrated that alpha4-integrin molecule plays a role in the early stages of PG-PS induced T lymphocyte migration to intestinal villus mucosa and Peyer's patches. By this study, we were able to demonstrate the chatnges in T lymphocyte-endothelial interaction after lymphocyte activation and obtained informations about their regulatory mechanisms.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Miura S. et al.: "Endotoxin stimulates lymphocyte-endothelial interactions in rat intestinal Peyers patches and villus mucosa." Am. J. Phystol.271. G282-G292 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Serizawa H. et al.: "Reversal of altered intestinal mucosal immunity in rats fed elemental diei by supplementation of oleic acid." J. Gastroenterol Hepatol. 11. 811-818 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fukumura D. et al.: "IL-1 is ar important mediator for microcirculatory changes in endotoxin-induced intestinal mucosal damage." Dig, Dis. Sci.41. 2482-2492 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miura S. et al.: "Vaso active intestinal peptide modulates T lymphocyte migration in peyer‘s pathes of rat smoll intestine." Am, J. Phystol.272. G92-G99 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanaka S et al.: "Amelioration of chronic inflammation by injestion of elemental diet in a rat model of granulomatous colitis." Dig, Dis. Sci.42. 408-419 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuzuki Y. et al.: "Enhanced lymphocyte interaction in postcapillary venules of peyer‘s patchesduringfat absorption in rats." Gastroenterology. 112. 813-825 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miura S. et al.: "Molecular mechanism of lymphocyte trafficking in peyer′s patches" Tsuchiya M et al eds Excerpta Medica(Tokyo) Organ Microctriulation, (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miura S. et al.: "Role of nitric oxide in lymphocyte-enclothelium interaction in peyer′s patches and villus mucosa of rat small intestine" Messmer K. et al eds. Monduzzi Editore(ttrly) Stxth World Congress for Microcirculation, (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miura, S., Tsuzuki, Y., Kurose, I., Suematsu, M., Shigematsu, T., Kimura, H., Higuchi, H., Serizawa, H., Yagita, H., Okumura, K., Granger, D.N.and Ishii, H.: "Endotoxin stimulates lymphocyte-endothelial interactions in rat intestinal Peyer's patches and villus mucosa." Am.J.Physiol.271 (Gastrointest.Liver Physiol.34). G282-G292 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Serizawa, H., Miura, S., Imaeda, H., Tanaka, S., Kimura, H., Tsuzuki, Y., Han, J-Y., Toda, K., Hamada, Y., Tsuchiya, M., and Ishii, H.: "Reversal of altered intestinal mucosal immunity in rats fed elemental diet by supplementation of oleic acid." J.Gastroenterol.Hepatol.11. 811-818 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fukumura, D., Miura, S., Kurose, I., Higuchi, H., Suzuki, H., Ebinuma, H., Han, J-Y., Watanabe, N., Wakabayashi, G., Kitajima, M.and Ishii, H.: "IL-1 is an important mediator for micricirculatory changes in endotoxin-induced intestinal mucosal damage." Dig.Dis Sci.41. 2482-2492 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miura, S., Serizawa, H., Tsuzuki, Y., Kurose, I., Suematsu, M., Higichi, H., Shigematsu, T., Hokari, R., Hirokawa, M., Kimura, H.and Ishii, H.: "Vasoactive intestinal peptide modulates T lymphocyte migration in Peyer's patches of rat small intestine." Am.J.Physiol.(Gastrointest.Liver Physiol.35). G92-G99 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanaka, S., Miura, S., Kimura, H., Ohkubo, N., Tsuzuki, Y., Fukumura, D., Serizawa, H., Kurose, I., Mori, M.and Ishii, H.: "Amelioration of chronic inflammation by injestion of elemental diet in a rat model of granulomatous enteritis." Dig.Dis Sci.42. 408-419 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuzuki, Y., Miura, S., Kurose, I., Suematsu, M., Higuchi, H., Shigematsu, T., Kimura, H., Serizawa, H., Hokari, R., Akiba, Y., Yagita, H., Okumura, K., Tso, P., Granger, D.N.and Ishii, H.: "Enhanced lymphocye interaction in postcapillary venules of Peyer's patches during fot absorption in rats." Gastroenterology. 112. 813-825 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimura, H., Miura, S., Shigematsu, T., Ohkubo, N., Tsuzuki, Y., Kurose, I., Higuchi, H., Akiba, Y., Hokari, R., Hirokawa, M., Serizawa, H.and Ishii, H.: "Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn's disease." Dig.Dis.Sci.42. 1047-1054 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hirokawa, M., Miura, S., Shigematus, T., Yoshida, H., Hokari, R., Higuchi, H., Kurose, I., Kimura, H., Saito, H., Nakaki, T.and Ishii, H.: "Pressure stimulates proliferation and DNA synthesis in rat intestinal epithelial cells." Life Sci.61. 667-672 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimura, H., Hokari, R., Miura, S., Shigematsu, T., Hirokawa, M., Akiba, Y., Kurose, I., Hiuchi, H., Fujimori, H., Tsuzuki, Y., Serizawa H.and Ishii, H.: "Increased expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in colonic mucosa of patients with active" Gut. 42. 180-187 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miura, S., Tsuzuki, Y., Hokari, R., Serizawa, H., Kurose, I., Hirokawa, M., Higuchi, H., Shigematsu, T., Kimura, H., Suematsu, M., Tsuchiya, M.and Ishii, H.: Organ Microcirculation : Bridging between Basic and Clinical Sciences., eds.by Tsuchiya, M., Katori, M., Suematsu, M."Molecular mechanism of lymphocyte trafficking in Peyer's patches.". Excerpta Medica (Tokyo), 29-36 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miura, S., Hokari, R., Tsuzuki, Y., Hirokawa, M., Kurose, I., Kimura, H., Serizawa, H., Suematsu, M., Yagita, H., Granger, D.N., Tsuchiya, M.and Ishii, H.: Sixth World Congress for Microcirculation, eds.by Messmer, K., Kubler, W.M., "Role of nitric oxide in lymphocyte-endothelium interaction in Peyer's patches and villus mucosa of rat small intestine.". Monduzzi Editore (Bologna, Italy), 637-641 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimori, H., Miura, S., Hokari, R., Hirokawa, M., Kimura, H., Takeuchi, T., Yoshida, H., Higuchi, H., Kurose, I., Suzuki, H., Tsuzuki, Y., Serizawa, H., Suematsu, M.and Ishii, H.: Microcirculation annual 1997, eds.by Tsuchiya, M., Asano, M., Sato, N."Migration of activated T lymphocytes to hepatic sinusoid.". Nihon Igakukan (Tokyo), 165-166 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miura,S.et al: "Vasoactive intestinal peptide modulates T lymphocyte migration in Peyer's patches of rat small intestine." Am.J.Physiol. (Gastrointest.Liver Physiol.). 272. G92-G99 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsuzuki Y.,Miura,S.et al: "Enhanced lymphocyte interaction in postcapillary venules of Peyer's patches during fat absorption in rats." Gastroenterology. 112. 813-825 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka,S.,Miura,S,et al: "Amelioration of chronic inflammation by injestion of elemental diet in a rat model of granulomatous enteritis." Dig.Dis.Sci.42. 408-419 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujimori H,Miura.S.et al: "Migration of activated T lymphocytes to hepatic sinusoid." Microcirculation annual 1997. 165-166 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 穂苅量太.三浦総一郎 他: "活性化Tリンパ球の腸粘膜におけるmigration動態" Prog.Med.17. 1956-1958 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Tsuzuki: "α_4integrin plays a critical role in early stages of T lymphocyte migration in Peyer's patches" Int.Immunol. 8. 287-295 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Miura: "Endotoxin stimulates lymphocyte-endothelial interaction in rat intestinal peyer's patches and villus mucosa" Am.J.Physiol. 271. G282-G292 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Serizawa: "Reversal of altered intestinal mucosal immunity in rats fed elemental diet by supplementation of oleic acid" J.Gastroenterol.Hepatol. 11. 811-818 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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