2000 Fiscal Year Final Research Report Summary
Role of CX_3C-chemokine, fractalkine on pathogenesis of periodontitis
| Project/Area Number |
11470464
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Periodontal dentistry
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| Research Institution | Osaka Dental University |
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Principal Investigator |
UMEHARA Hisanori OSAKA DENTAL UNIVERSITY, LECTURE, 歯学部, 講師 (70247881)
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| Co-Investigator(Kenkyū-buntansha) |
DOMAE Naochika OSAKA DENTAL UNIVERSITY, PROFESSOR, 歯学部, 教授 (60115889)
IMAI Toshiiio KAN RESEARCH INSTITUTE, HEAD, プロジェクト2, 主任研究員
KONO Takeshi NIPPON BOEHRINGER INGELHEIM, HEAD, 主任研究員
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| Project Period (FY) |
1999 – 2000
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| Keywords | NK cells / CD2 / signal pathway / cytotoxicity / tyrosine kinase / adapter proteins / PI 3-kinase |
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| Research Abstract |
Periodontitis is the chronic inflammation caused by oral bacteria, such as Porphyromonas gingivalis in dental plaque. Accumulation of immunocompetent cells, such as T cells, NK cells and macrophages in the inflammatory gingiva may be involved in the pathogenesis. The vascular endothelium plays an important role in the recruitment and migration of circulating effector cells into sites of inflammation and immune response. Fractalkine, a recently identified chemokine is expressed in a membrane-bound form on TNF-α-and IL-1-activated endothelial cells. We examined the molecular and biological functions of fractalkine on adhesion between effector cells and endothelial cells, and found the following evidences :
1.CX_3C-chemokine, fractalkine enhanced adhesion of THP-1 cells to endothelial cells through integrin-dependent and independent mechanisms (Reference 1). THP-1 cells express mRNA encoding a receptor for fractalkine, CX_3CR1, determined by northern blotting and Scatchard analysis. Soluble-fractalkine enhanced adhesion of THP-1 cells to fibronectin and ICAM-1 in a dose-dependent manner.
2.Fractalkine-mediated endothelial cell injury by NK cells (Reference 2). Freshly separated NK cells expressed the fractalkine receptor (CX_3CR1) determined by FACS analysis. Soluble fractalkine enhanced NK cell cytolytic activity against K562 target cells. Transfection of fractalkine cDNA into ECV304 cells or HUVECs resulted in increased adhesion of NK cells and susceptibility to NK cell-mediated cytolysis compared to control transfection.
3.CX_3C-chemokine, fractalkine functions predominantly as an adhesion molecule in monocytic cell line, THP-1 (Reference 3). Co-immobilized fractalkine with fibronectin or ICAM-1 enhanced adhesion of THP-1 cells, which express the fractalkine receptor (CX_3CR1), compared beyond that observed with each alone. However, soluble fractalkine induced little chemotaxis in THP-1 cells in comparison to MCP-1 which induced a strong chemotactic response.
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