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

近年来，越来越多的证据表明发酵支原体是类风湿关节炎(RA)的致病微生物。此前，我们报道了含有磷胆碱的甘油三脂(GGPL)的发现和结构测定，GGPL-I和GGPL-III是发酵支原体的主要脂类抗原，是一种特异性免疫决定蛋白。我们提出，由于GGPL具有很强的免疫原性，并与哺乳动物含磷胆碱的甘油三脂(GGPL-I和GGPL-III)具有很强的免疫原性和分子模拟，因此我们在类风湿关节炎患者的滑膜组织中存在GGPL-HI抗原，我们已经针对GGPL-HI抗原制作了特异性的克隆抗体。GGPL-III可显著诱导健康志愿者外周血单核细胞产生IL-6和肿瘤坏死因子-α，并促进类风湿关节炎滑膜成纤维细胞的增殖。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，发酵支原体的GGPL-III作为一种持久性病原体，在类风湿关节炎的炎症发生和延续中起着重要的作用，也可以作为诊断标记物。我们制备了GGPL及其纯化系统，用于生物功能研究，分析GGPL的病理功能。此外，所建立的抗发酵支原体GGPL-III的单抗可用于发酵支原体GGPL相关疾病的分析。GGPL抗原的结构被很好地表征，这对于进一步研究分子机制、设计免疫系统调节策略和药物开发是有利的。

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.