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Effects of heparin-like glycosaminoglycans on postoperative complications

Research Project

Project/Area Number 09671250
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionShowa University

Principal Investigator

SANADA Yutaka  Showa University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70103893)

Co-Investigator(Kenkyū-buntansha) YAMAGUCHI Masahiko  Showa University Faculty of Medicine, Assistant Professor, 医学部, 講師 (00266149)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsEndotoxin / Neutrophils / HUVEC / Selectin / Adhesion / Dextran sulfate / 細胞接着 / 糖鎖薬剤 / 抗炎症効果
Research Abstract

Increased levels of endotoxin in the blood can lead to various fatal conditions including septic shock and adult respiratory distress syndrome because of the systemic inflammatory response to endotoxiri. One of the most important aspects of the inflammatory process involves adhesion of leukocytes to vascular endothelial cells (ECs). The initial step in the adhesion is BC activation which induces expression of adhesion molecules including E-selectin . This step results in increased leukocyte rolling along ECs, which is mediated by selectins and carbohydrate ligands. Heparin-like glycosaminoglycans (h-GAGs) have been reported to have anti-inflammatory effects and we investigated the effect of h-GAGs on neutrophil adhesion to ECs stimulated by endotoxin (Iipopolysaccharide, LPS) under nonstatic conditions, the molecules involved in the adhesion, and the mechanisms of the inhibitory action of h-GAGs. Neutrophil adhesion to Iipopolysaccharide-activated ECs was assayed under rotating conditions with addition of h-GAGs or monoclonal antibodies (mAbs) against selectins. Neutrophil adhesion to activated ECs under rotating conditions was suppressed completely by anti-E-selectin mAb and partially by anti-L-selectin mAb. Addition of dextran sulfate or heparin also significantly inhibited neutrophil adhesion to ECs under the same conditions. Moreover, effects of h-GAGs on neutrophil adhesion to recombinant E-selectin-coated plates were analyzed. Anti-E-selectin mAb and dextran sulfate, but not heparin, significantly inhibited neutrophil adhesion to E-selectin-coated plates. Results suggest that dextran sulfate inhibited E-selectin-mediated neutrophil adhesion to endotoxin-activated ECs under physiologic flow conditions.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Yamaguchi M, et al.: "Selective inhibition of vascular cell adhesion molecule-1 expression by verapamil in human vascular endothelial cells" Transplantation. 63. 759-764 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuzume M, et al.: "A monoclonal antibody against ICAM-1 suppressed hepatic ischemia-reperfusion injury" Eur.Surg.Res.29. 93-100 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakano H, et al.: "The effects of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver----" HEPATOLOGY. 26. 670-678 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sanada Y, et al.: "Endoscopic sphincterotomy and laparoscopic cholecystectomy in an infant with cholecysto-choledocholithiasis" J.Pediatr.Surg.33. 1312-1314 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi M, et al.: "Dextran sulfate inhibits E-selectin-mediated neutrophil adhesion to endotoxin-activated vascular endothelial cells" Life Sci. 64. 9-17 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi M, et al.: "The Effect of flow on the neutrophil-mediated Ca2+ responses in human vascular endothelial cells stimulated by endotoxin" Surg.Today. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi M,et al.: "Selective inhibition of vascular cell adhesion molecule-1 expression by verapamil in human vascular endothelial cells" Transplantation. 63. 759-764 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuzume M,et al.: "A monoclonal antibody against ICAM-1 suppressed hepatic ischemia-reperfusion injury" Eur.Surg.Res.29. 93-100 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakano H,et al.: "The effects of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet" HEPATOLOGY. 26. 670-678 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sanada Y,et al.: "Endoscopic sphincterotomy and laparoscopic cholecystectomy in an infant with cholecysto-choledocholithiasis" J.Pediatr.Surg.33. 1312-1314 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi M,et al.: "Dextran sulfate inhibits E-selectin-mediated neutrophil adhesion to endotoxin-activated vascular endothelial cells" Life Sci. 64. 9-17 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi M,et al.: "The Effect of flow on the neutrophil-mediated Ca2+ responses in human vascular endothelial cells stimulated by endotoxin" Surg.Today. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sanada Y,et al: "Endoscopic sphincterotomy and laparoscopic chole cystectomy in an intant with cholecysto-choledocholithiasis" J.Pediatr.Surg.33. 1312-1314 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamaguchi M,et al: "Dextran sulfate inhibits E-selectin-mediated neutrophil adhesion to endotoxin-activated vascular endothelial cells" Life Sci. 64. 9-17 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamaguchi M,et al.: "Selective inhibition of vascular cell adhesion molecule-1 expression in human vascular endothelial cells." Transplantation. 63. 759-764 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamaguchi M,et al.: "Effects of flow on neutrophil-mediated Ca2+response in human vascular endothelial cells." Inflamm.Res.46. S227 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakano H, Yamaguchi M,et al.: "The effects of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet" HEPATOLOGY. 26. 670-678 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sanada Y, Yamaguchi M,et al.: "Allopurinol reduced hepatic ischemia-reperfusion injury exacerbated by inhalation of high-concentration oxygen in rats." Eur.Surg.Res.29. 429-437 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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