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Molecular mechanisms underlying lymphocyte-specific cell trafficking into lymph nodes-Functional analysis of genes specifically expressed in high endothelial venules (HEV)

Research Project

Project/Area Number 11470057
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionOsaka University

Principal Investigator

MIYASAKA Masayuki  Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (50064613)

Co-Investigator(Kenkyū-buntansha) MURAI Toshiyuki  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20311756)
KAWASHIMA Hiroto  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50260336)
TANAKA Toshiyuki  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (30217054)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2000: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1999: ¥7,500,000 (Direct Cost: ¥7,500,000)
Keywordslymphocyte homing / high endothelial venule / chemokine / lymph node / endothelial cell / sulfotransferase / 接着分子 / 組織特異的遺伝子 / cDNAライブラリー / リンパ球
Research Abstract

We have successfully isolated endothelial cells from HEV (HEV cells) of peripheral and mesenteric lymph nodes of mice and constructed HEV-specific 3'-end cDNA libraries. We then randomly sequenced about 1,500 cDNA clones from each library and compared the obtained nucleotide sequences with those found in 30 different cDNA libraries similarly obtained from other tissues and also with those registered in the EST database. From this analysis, we found several molecules selectively expressed by HEV cells but not normal endothelial cells. They include mac25/TAF/PSF, SGP-2, DARC, leucine-rich α2 glycoprotein and Ig-hepta. In addition, a few chemokines such as SLC, ELC, BLC, fractalkine, KC and lymphotactin are expressed by HEV at mRNA and protein levels. These chemokines except KC can attract selective lymphocyte subsets in vitro, and hence are strategically useful for recruiting these subsets into lymph nodes. In addition, in collaboration with Prof.M.Minoru of La Jolla, we have successfully cloned a novel GlcNAc-6-O-sulfotransferase selectively expressed inHEV.This enzyme is essential for the formation of an L-selectiin binding sugar moiety, 6-sulfo sialyl Lewis X, and is likely to play a crucial role in the L-selectin-dependent lymphocyte homing into lymph nodes.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Izawa,D.: "Expression profile of active genes in mouse lymph node high endothelial cells."Int.Immunol.. 11. 1989-1997 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Pabst,R.: "Lymphocyte migration. More than an interaction of lymphocytes with endothelial cells of the high endothelial venules via adhesion molecules."The Immunologist. 7. 1-2 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Luo,Z.: "Analysis of the mode of action of a novel immunosuppressant FTY720 in mice."Immunopharmacology. 41. 199-207 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanoh,N.: "Constitutive expression of GlyCAM-1 core protein in the rat cochlea."Cell Adhes.Commun.. 7. 259-256 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiraoka,N.: "A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl Lewis^x, an L-selectin ligand displayed by CD34."Immunity. 11. 79-89 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Majuri,M.-L.: "High endothelial cells synthesize and degrade sLex. Putative implications for L-selectin-dependent recognition."FEBS Letters. 455. 97-100 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iizuka,T.: "Stage-specific expression of mucosal addressin cell adhesion molecule-1 during embryogenesis in rats."J.Immunol.. 164. 2463-2471 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishimura,T.: "Mammary glands of aly mice : Developmental changes and lactation-related expression of specific proteins, α-casein, GlyCAM-1 and MAdCAM-1."Amer.J.Reprod.Immunol.. 43. 351-358 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ding,Z.: "Sulfatide binding and activation of leukocytes through an L-selectin-independent pathway."J.Leuk.Biol.. 68. 65-72 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Izawa, D., Tanaka, T., Saito, K., Ogihara, H., Usui, T., Kawamoto, S., Matsubara, K., Okubo, K.& Miyasaka, M.: "Expression profile of active genes in mouse lymph node high endothelial cells."Int.Immunol.. 11. 1989-1997 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Pabst, R.& Miyasaka, M.: "Lymphocyte migration. More than an interaction of lymphocytes with endothelial cells of the high endothelial venules via adhesion molecules."The Immunologist. 7. 1-2 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Luo, Z, Tanaka, T., Kimura, F.& Miyasaka, M.: "Analysis of the mode of action of a novel immunosuppressant FTY720 in mice."Immunopharmacology. 41. 199-207 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanoh, N., Dai, C.-F., Tanaka, T., Izawa, D., Li, Y.-F., Kawashima, H.& Miyasaka, M.: "Constitutive expression of GlyCAM-1 core protein in the rat cochlea."Cell Adhes.Commun.. 7. 259-266 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiraoka, N., Petryniak, B., Nakayama, J., Tsuboi, S., Suzuki, M., Yeh, J-C., Izawa, D., Tanaka, T., Miyasaka, M., Lowe, J.B.& Fukuda, M.: "A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl Lewis^x, an L-selectin ligand displayed by CD34."Immunity. 11. 79-89 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Majuri, M.-L., Rabina, J., Niittymaki, J., Tiisala, S., Mattila, P., Aavik, E., Miyasaka, M., Renkonen, O.& Renkonen, R.: "High endothelial cells synthesize and degrade sLex. Putative implications for L-selectin-dependent recognition."FEBS Letters. 455. 97-100 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iizuka, T., Tanaka, T., Suematsu, M., Miura, S., Watanabe, T., Koike, R., Ishimura, Y., Ishii, H., Miyasaka, N.& Miyasaka, M.: "Stage-specific expression of mucosal addressin cell adhesion molecule-1 during embryogenesis in rats."J.Immunol.. 164. 2463-2471 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishimura, T., Koike, R.& Miyasaka, M.: "Mammary glands of aly mice : Developmental changes and lactation-related expression of specific proteins, α-casein, GlyCAM-1 and MAdCAM-1."Amer.J.Reprod.Immunol.. 43. 351-358 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ding, Z., Kawashima, H.& Miyasaka, M.: "Sulfatide binding and activation of leukocytes through an L-selectin-independent pathway."J.Leuk.Biol.. 68. 65-72 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Izawa,D.: "Expression profile of active genes in mouse lymph node high endothelial cells."Int.Immunol.. 11. 1989-1997 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Pabst,R.: "Lymphocyte migration. More than an interaction of lymphocytes with endothelial cells of the high endothelial venules via adhesion molecules."The Immunologist. 7. 1-2 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Luo,Z.: "Analysis of the mode of action of a novel immunosuppressant FTY720 in mice."Immunopharmacology. 41. 199-207 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kanoh,N.: "Constitutive expression of GlyCAM-1 core protein in the rat cochlea."Cell Adhes.Commun.. 7. 259-256 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hiraoka,N.: "A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl Lewis^x, an L-selectin ligand displayed by CD34."Immunity. 11. 79-89 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Majuri,M.-L.: "High endothelial cells synthesize and degrade sLex.Putative implications for L-selectin-dependent recognition."FEBS Letters. 455. 97-100 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iizuka,T.: "Stage-specific expression of mucosal addressin cell adhesion molecule-1 during embryogenesis in rats."J.Immunol.. 164. 2463-2471 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishimura,T.: "Mammary glands of aly mice : Developmental changes and lactation-related expression of specific proteins, α-casein, GlyCAM-1 and MAdCAM-1."Amer.J.Reprod.Immunol.. 43. 351-358 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ding,Z.: "Sulfatide binding and activation of leukocytes through an L-selectin-independent pathway."J.Leuk.Biol.. 68. 65-72 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Izawa,D.: "Expression profile of active genes in mouse lymph node high endothelial cells"Int.Immunol.. 11. 1989-1997 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iizuka,T.: "Stage-specific expression of mucosal addressin cell adhesion molecule-1 during embryogenesis in rats"J.Immunol.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishimura,T.: "Mammary gland of aly mice : Developmental changes and lactation-related expression of specific proteins,α-casein, GlyCAM-1 and MAdCAM-1"Amer.J.Reprod.Immunol.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishiwatari-Hayasaka,H.: "Requirements for signal delivery through CD44 : Analysis using CD44-Fas chimeric proteins"J.Immunol.. 163. 1258-1264 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Goda,K.: "Characterization of an apparently conserved epitope in E-and P-selectin identified by dual-specific monoclonal antibodies"Eur.J.Immunol.. 29. 1551-1560 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Pabst,R.: "Lymphocyte migration. More than an interaction of lymphocytes with endothelial cells of the high endothelial venules via adhesion molecules"The Immunologist. 7. 1-2 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawashima,H: "Identification and characterization of ligands for L-selectin in the kidney. I.. Versican, a large chondoroitin sulfate proteoglycan, is a ligand for L-selectin"Int.Immunol.. 11. 393-405 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Li,Y.-F.: "Identification and characterization of ligands for L-selectin in the kidney.II.. Expression of chondroitin sulfate and heparan sulfate proteoflycans reactive with L-selectin"FEBS Letters. 444. 201-205 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Watanabe,N.: "Identification and characterization of lifands for L-selectin in the kidney.III.Characterization of L-selectin reactive heparan sulfate proteoglycans"J.Biochem.. 125. 826-831 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiraoka,N.: "A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialy Lewis^x,an L-selection ligand displayed by CD34"Immunity. 11. 79-89 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirose,M.: "A functional epitope on P-selectin that supports binding of P-selectin to P-selectin glycoprotein ligan-1 but not to sialyl Lewis X oligosaccharides"Int.Immunol.. 10. 639-649 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsuzuki,S.: "FK506(tacrolimus) inhibits extravasation of lymphoid cells by abrogating VLA-4/VCAM-1 mediated transendothelial migration"FEBS Letters. 430. 414-418 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsuzuki,S.: "Intracellular signal-transducing elements involved in transendothelial migration of lymphoma cells"89. 571-577 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawashima,H.: "Vascular and non-vascular ligands for L-selectin"Cell Adhes.Commun.. 6. 135-139 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iizuka,T.: "Cloning and characterization the rat MAdCAM-1 Cdna and gene"Biochim.Biophys.Acta. 1395. 266-270 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyasaka,M.: "Selectins(CD62/E/L/P)"Encyclopedia of Immunology. 2158-2161 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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