2002 Fiscal Year Final Research Report Summary
Host-pathogen interaction at lipid microdomains based on the structural analyses of glycophospholipid antigens
| Project/Area Number |
13670329
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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 |
Immunology
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| Research Institution | National Cancer Center Research Institute |
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Principal Investigator |
MATSUDA Kazuhiro National Cancer Center Research Institute, Stuff scientisty, 薬効試験部, 主任研究官 (80251502)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Yoshihiro Nagoya University, Associate Professor, 工学研究科, 助教授 (80183896)
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| Project Period (FY) |
2001 – 2002
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| Keywords | lipid microdomain / mycoplasma / glycolipids / phospholipids / ganglioside / dendritic cell / host-pathogen interaction |
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| Research Abstract |
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.
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