| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Antiphospholipid syndrome (APS) is an autoimmune disorder clinically characterized by recurrent thromboses and pregnant morbidity as well as positive for antiphospholipid antibodies (aPL) including anticardiolipin antibody (αCL) and lupus anticoagulant (LA). To determine which adhesion molecules are essential in the induction of aPL, we attempted to induce APS in the mice deficient of several kinds of adhesion molecules including L-selectin, P-selectin, E-selection, ICAM-1, and L-selectin/ICAM-1, and evaluated aPL production and thrombogenesity in the mice. C57BL/6 mice were injected with purified 20 μg of β2-glycoprotein I (β2-GPI) to pedal pad twice at a 3 week interval with Freund's adjuvant. Six weeks after the first injection of β2-GPI, wild-type mice developed thrombocytopenia, prolongation of APTT, and elevation of aCL titer, while the mice injected only with Freund's adjuvant did not show these changes (p < 0.005, <0.005, and < 0.01, respectively). The percentage of glomerular fibrin deposit (%GFD) induced by the injection of 5 mg/kg of lipopolysaccharide (LPS) increased significantly in the APS mice compared to the control mice (p < 0.01). All adhesion-molecule KO mice except for E-selectin KO mice developed thrombocytopenia, APTT prolongation, high aCL titers, and positivity for aPL after repeated injection of β2-GPI, though %GFD did not increase significantly in these mice compared to control mice. In contrast, E-selectin-KO mice did not develop any changes in platelet counts, APTT, aCL titer, and %GFD after injection of 62-GPI. These findings indicated that, although several adhesion molecules may be involved in the development of thrombosis in APS-model mice, E-selectin has a key role in the induction of aPL.
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