1998 Fiscal Year Final Research Report Summary
Effects of heparin-like glycosaminoglycans on postoperative complications
| Project/Area Number |
09671250
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Showa University |
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Principal Investigator |
SANADA Yutaka Showa University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70103893)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Masahiko Showa University Faculty of Medicine, Assistant Professor, 医学部, 講師 (00266149)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Endotoxin / Neutrophils / HUVEC / Selectin / Adhesion / Dextran sulfate |
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| 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.
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