2002 Fiscal Year Final Research Report Summary
INTERVENTION OF AUTOANTIBODY IN THE MEMBRANE PHOSPHOLIPID FLIP-FLOP OF TROPHOBLAST CELLS.
| Project/Area Number |
13670239
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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 |
Experimental pathology
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| Research Institution | RESEARCH INSTITUTE, OSAKAMEDICAL CENTER FOR MATERNAL AND CHILD HEALTH |
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Principal Investigator |
WADA Yoshinao RESEARCH INSTITUTE, OSAKAMEDICAL CENTER FOR MATERNAL AND CHILD HEALTH, DEPARTMENT OF MOLECULAR MEDICINE, DIRECTOR, 代謝部門, 部長 (00250340)
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| Project Period (FY) |
2001 – 2002
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| Keywords | ANTIPHOSPHOLIPD ANTIBODY / PHOSPHATIDYLSERINE / THROMBOSIS / COMPLEMENT / FACTOR H |
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| Research Abstract |
Antiphospholipid antibody is an autoantibody associated with antiphospholipid syndrome (APS) representing arterial and venous thrombosis, thrombocytopenia, and recurrent fetal loss. The underlying mechanism of these complications is not fully understood, while they are obviously due to accelerated coagulation. Since a negatively charged phospholipid, phosphatidylserine, which potentially triggers blood coagulation, is exposed to the outer leaflet of plasma membrane during apoptosis and trophoblast differentiation, we focused on the proteins binding to negatively charged phospholipids in order to delineate the pathogenesis of APS. An affinity column, in which cardiolipin or phosphatidylserine was embedded in octyl cellulose was prepared, and the plasma proteins bound to these phospholipids were collected by elution with 2M NaCl. A proteins were separated by iD or 2D electrophoresis, and then identified by peptide mass fingerprinting. The proteins included beta2 glycoprotein I, inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP), complement factor 4, factor H and factor H-related protein I. The binding of factor H was interesting, since factor H mutations cause hemolytic uremic syndrome with characteristic pathology of renal microvascular thrombosis, which also occurs in APS. Recently, the crucial role of alternative complement pathway activation has been reported. Thus, possible involvement of factor H, a regulatory protein of alternative pathway, would be an attractive speculation to delineate the pathogenesis of APS.
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