Potentiation of T Cell Function by a Marine Algae-Derived Sulfated Polymannuroguluronate : In Vitro Analysis of Novel Mechanisms
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概要
- 論文の詳細を見る
Marine algae-derived sulfated polymannuroguluronate (SPMG), a candidate drug for AIDS treatment, was intraperitoneally injected into normal mice for 6 weeks, and the in vivo and in vitro mechanisms of SPMG for immunomodulation were investigated in isolated lymphocytes by MTT assay, flow cytometry, and surface plasmon resonance assay. SPMG treatment at 5 and 10 mg/kg enhanced concanavalin A (ConA)-induced T cell proliferation, cellular levels of CD69, interleukin-2 (IL-2), and interferon-γ (IFN-γ), as well as CD4/CD8 ratio, while decreasing tumor necrosis factor-α (TNF-α) level in T cells of peripheral blood mononuclear cells. In addition, 1 molecule of SPMG bound to 2/3 molecules of IL-2 with a KD of 9.53 × 10−7 M. Heparin prevented SPMG binding to IL-2 by 72.2%; thus, to a large extent, SPMG and heparin share common binding sites on IL-2. In contrast, other glycosaminoglycans (e.g., chondroitin sulfate and dermatan sulfate) had little effect on SPMG and IL-2 interaction, suggesting the requirement of a defined sequence within the sugar chain for specific recognition of IL-2. Concomitant treatment of IL-2 and SPMG augmented lymphocyte proliferation, compared with IL-2 alone; in contrast, SPMG alone had no proliferative effect. Taken together, our findings demonstrated for the first time that SPMG exerted its immunomodulation by direct activation of T cell function, accompanied by simultaneous modulation of cytokine function, which suggests that SPMG would show great promise for use in anti-AIDS therapy.
- 社団法人 日本薬理学会の論文
- 2005-01-20
著者
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Xia Wei
中華人民共和国
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Xia Wei
Department Of Pharmacology Marine Drug And Food Institute Ocean University Of China
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Li Jing
中華人民共和国
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Li Jing
Department Of Pharmacology Marine Drug And Food Institute Ocean University Of China
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GENG Meiyu
Department of Pharmacology, Marine Drug and Food Institute, Ocean University of China
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XIN Xianliang
Department of Pharmacology, Marine Drug and Food Institute, Ocean University of China
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DING Jian
Shanghai Institute of Materia Medica, Chinese Academy of Sciences
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Xin Xianliang
Department Of Pharmacology Marine Drug & Food Institute Ocean University Of China
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Xin Xianliang
中華人民共和国
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Ding J
Shanghai Institute Of Materia Medica Chinese Academy Of Sciences
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Ding Jian
Institute Of Materia Medica Shanghai Institute For Biological Science Chinese Academy Of Sciences
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Geng Meiyu
Department Of Pharmacology Marine Drug & Food Institute Ocean University Of China
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Ding Jian
Shanghai Institute Of Materia Medica Chinese Academy Of Sciences
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Li J
Department Of Pharmacology Marine Drug And Food Institute Ocean University Of China
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Li Jing
Department Of Agriculture Faculty Of Agriculture Kochi University
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Geng Meiyu
Department of Marine Pharmacology, Marine Drug and Food Institute, Ocean University of China
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