Host-pathogen interaction at lipid microdomains based on the structural analyses of glycophospholipid antigens

基于糖磷脂抗原结构分析的脂质微区宿主-病原体相互作用

• 批准号: 13670329
• 负责人: MATSUDA Kazuhiro
• 金额: $ 1.6万
• 依托单位: National Cancer Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670329/
• 关键词: lipid microdomain; mycoplasma; glycolipids; phospholipids; ganglioside; dendritic cell; host-pathogen interaction; 光学異性体

Recently, evidences that Mycoplasma fermentans can be a pathogenic microorganism of rheumatoid arthritis (RA), have been accumulated. Previously, we reported the finding and structural determination of phosphocholine-containing glycoglycerolipids (GGPLs: GGPL-I and GGPL-III), which are specific immunodeterminats and are the major lipid antigens of Mycoplasma fermentans.We have been proposed that they are playing roles as immunodisturbing agents in cell functions such as inflammation and cell differentiation, because the GGPLs have strong immunogenicity and molecular mimicry with mammalian phosphocholine-containing lipids, such as phosphatidyicholine, sphingomyelin, platelet-activating factor (PAF).We showed the existence of GGPL-HI antigen, to which we had made specific monoclonal antibody, in synovial tissues from rheumatoid arthritis patients. GGPL-III significantly induced IL-6 and TNF-α production in peripheral blood mononulear cells from healthy volunteers and proliferation of rheumatoid arthritis synovial fibroblasts. Also we, found that anti-GGPL-III antibodies were detected 25.6 %(1O/39) of rheumatoid arthritis patient's sera. These findings demonstrate that GGPL-III of M. fermentans, as a persistent pathogen, play an important role in initiating and perpetuating inflammation of rheumatoid arthritis and also could be a diagnostic marker.We have prepared chemically synthesized of GGPLs and its purification system for biofunctional study to analyze pathological functions of GGPLs. And also established monoclonal antibody against M fermentans GGPL-III may be useful for the analysis of M. fermentans GGPLs-related disorders. The structure of the GGPL antigens are well characterized, is an advantage for the further study of molecular mechanisms, for devising strategies for regulation of the immune system and for drug discovery.

近年来，发酵支原体可能是类风湿关节炎（RA）的致病微生物的证据越来越多。在此之前，我们报道了含磷酸胆碱的糖甘脂的发现和结构测定（GGPL：GGPL-I和GGPL-III）是发酵支原体的主要脂质抗原，是特异性免疫决定因子，在炎症和细胞分化等细胞功能中起免疫干扰作用，由于GGPLs具有很强的免疫原性和与哺乳动物含磷酸胆碱脂质如磷脂酰胆碱、鞘磷脂、血小板活化因子（PAF）的分子模拟性，我们证明了GGPL-HI抗原的存在，我们在类风湿性关节炎患者的滑液组织中制备了特异性单克隆抗体。GGPL-III显著诱导健康志愿者外周血单核细胞产生IL-6和TNF-α，并诱导类风湿关节炎滑膜成纤维细胞增殖。在39例类风湿关节炎患者血清中，抗GGPL-Ⅲ抗体阳性率为25.6%（10/39）。这些结果表明，M.本研究通过化学合成GGPLs及其纯化系统，对GGPLs的病理功能进行了研究。本研究建立的抗发酵支原体单克隆抗体GGPL-Ⅲ可用于发酵支原体的分析。发酵性GGPL相关病症。GGPL抗原的结构被很好地表征，对于进一步研究分子机制、设计用于调节免疫系统的策略和药物发现是有利的。

项目成果

Matsuda, K., Saito, M., Yamamoto, N: "Encyclopedia of life sciences Vol.1 748-755 Antigen: lipid"Macmillan reference lt d(Nature publishing group). (2002)

Matsuda, K.、Saito, M.、Yamamoto, N：“生命科学百科全书 Vol.1 748-755 抗原：脂质”Macmillan Reference lt d（自然出版集团）。

松田和洋: "第4回21世紀の境界領域を考えるシンポジウム リウマチ新規診断・治療薬の開発:慢性関節リウマチの関節"Boundary. 28. 1-10 (2003)

Kazuhiro Matsuda：“21 世纪第四届边界领域研讨会：风湿病新诊断和治疗药物的开发：类风湿性关节炎的关节”边界。

松田 和洋: "Mycoplasma fermentans特異的糖リン脂質抗原の構造解析とその意義"日本マイコプラズマ学会誌. 28. 1-10 (2001)

Kazuhiro Matsuda：“发酵支原体特异性糖磷脂抗原的结构分析及其意义”日本支原体学会杂志 28. 1-10 (2001)。

松田和洋: "Mycoplasma fermentans特異的糖リン脂質抗原の構造解析とその意義"日本マイコプラズマ学会誌. 28. 1-10 (2001)

Kazuhiro Matsuda：“发酵支原体特异性糖磷脂抗原的结构分析及其意义”日本支原体学会杂志 28. 1-10 (2001)。

Matsuda, K., Matsuda, S., Saito, M., Ito, Y: "Separation of phospholipids and glycolipids using analytical toroidal-coil countercurrent chromatography. I. Separation of human brain lipids"J. Liq. Chrom. & Rel. Technol.. 25. 1267-1281 (2002)

Matsuda, K.、Matsuda, S.、Saito, M.、Ito, Y：“使用分析型环形线圈逆流色谱法分离磷脂和糖脂。I. 人脑脂质的分离”J。