| Project/Area Number |
09672218
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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 |
Biological pharmacy
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| Research Institution | Hoshi University |
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Principal Investigator |
TSUJI Tsutomu Hoshi University, Professor, 薬学部, 教授 (00143503)
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| Co-Investigator(Kenkyū-buntansha) |
IRIMURA Tatsuro University of Tokyo, Professor, 大学院・薬学系研究料, 教授 (80092146)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Sialyl Lewis X / leukocyte / Cell adhesion / Glycoprotein / Oxygen radical / Cytokine / Selectin / 細胞表面糖鎖 |
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| Research Abstract |
The purpose of this research project was the elucidation of a variation of sialyl Lewis X (sLeX) carbhohydrate chains on leukocyte membranes and their roles in the selectin-dependent cell adhesion and leukocyte activation.
(1) The production of tumor necrosis factor (TNF) in human blood monocytes was induced by monoclonal antibodies against sLeX carbohydrate chains. Several antibodies with different classes and binding specificities examined had distinct potency in the monocyte activation. In addition, the induction was partially inhibited by the pretreatment of monocytes with an anti-PSGL-l (P-selectin glycoprotein ligand-l) antibody.
(2) P-selectin-dependent adhesion of leukocytes was not necessarily correlated with the total expression levels of sLeX carbohydrate chains on their cell surface, but correlated with the amounts of sLeX antigen linked to PSGL- 1.
(3) Human blood neutrophils produced superoxide anion when they were incubated with immobilized P-selectin. The distribution sLeX epitopes was examined by fluorescent microscopy, and they were found to form a cluster at the cell attachment site.
These results suggest that the selectin-dependent leukocyte adhesion and functional activation were basically mediated by the interaction of sLeX carbohydrate chains with selectins and were influenced by a variation of the carbohydrate ligands, the nature of the carbohydrate-carrier molecules and their localization on cell membranes.
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