| Project/Area Number |
16390123
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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 |
Experimental pathology
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| Research Institution | Osaka Medical Center and Research Institute for Maternal and Child Health |
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Principal Investigator |
WADA Yoshinao Osaka Prefectural Hospital Organization, Osaka Medical Center and Research Institute for Maternal and Child Health, Department of Molecular Medicine, Director, 代謝部門, 所長兼部長 (00250340)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBUKAWA Yukinao Osaka Prefectural Hospital Organization, Osaka Medical Center and Research Institute for Maternal and Child Health, Department of Molecular Medicine, Research Scientist, 代謝部門, 研究員 (90393264)
NAKAMURA Orie Osaka Prefectural Hospital Organization, Osaka Medical Center and Research Institute for Maternal and Child Health, Department of Molecular Medicine, Post-doctoral Fellow, 代謝部門, 流動研究員 (40399613)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2006: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | antiphospholipid antibody / beta2 glycoprotein I / placenta / complement / extracellular matrix / 着床 / 細胞融合 / マトリックスメタロプロテアーゼ / 白血球 / 不妊症 |
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| Research Abstract |
It is generally accepted that the primary event of antiphohpholipid syndrome (APS) is the activation of the complement system. We carried out a proteomic analysis of the plasma proteins that are binding to negatively charged phospholipids, cardiolipin (CL) or phosphatidylserine (PS), and are thus potentially involved in the pathogenesis. The plasma proteins recovered from an Octyl-Sepharose column, in which CL or PS was embedded, were separated by two-dimensional electrophoresis. By peptide mass fingerprinting, factor H, factor H-related protein-1, IHRP, Complement 4, complement C1q and beta2 glycoprotein I were identified. A group of APS patients was demonstrated to have anti-factor H antibodies, but a close link of anti-factor H to the thrombotic or obstetric complications was not clearly demonstrated. These proteins are now being studied for their capability of inducing hemolysis of rabbit reticulocytes in the presence of antiphospholipid IgG from the APS patients.
Miscarriage is one
… More
of the complications found in APS patients. From this point of view, implantation may be a target of antiphospholipid antibodies. Matrix metalloproteinases (MMPs) have been implicated in embryonal implantation processes such as trophoblast invasion and decidualization. Therefore, temporal and spatial distributions of MMP bioactivities were analyzed by in situ zymography, which indicated these activities to be markedly increased in the post-coital mouse uterus as compared with the later implantation stage. Activity was ascribed to proMMP9, which moved from the uterine serosa to the endometrium but was not associated with mRNA upregulation. The activity was co-localized with infiltrating neutrophils, and neutropenic mice did not exhibit MMP9 expression. Removing the seminal vesicles from male mice abolished the post-coital increase in MMP9 in the female. These results indicate the major MMP activity in the preimplantation uterus to originate in proMMP9-bearing neutrophils attracted by seminal plasma. Considering our results together with those of previous reports of reduced fertility in Mmp9-deficient female mice, we speculate that neutrophil infiltration participates in the extracellular matrix degradation needed to support pregnancy. Less
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