1997 Fiscal Year Final Research Report Summary
Pathogenity of anti-cardiolipin antibodies : Reactivity to thrombomodulin
| Project/Area Number |
07670541
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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 |
内科学一般
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| Research Institution | Juntendo University School of Medicine |
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Principal Investigator |
KOBAYASHI Shigeto Juntendo University School of Medicine, Lecture, 医学部, 講師 (40186739)
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| Project Period (FY) |
1995 – 1997
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| Keywords | anti-cardiolipin antidodies / thrombomodulin / New Zealand mice / monoclonal antibody / affinity / pathogeneity / autoantibody / endothelial calls |
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| Research Abstract |
The reactivity with and affinity for thrombomodulin (TM) of monoclonal anticardiolipin antibodies (MoaCL), derived from a NZB x NZW (NZB/W) F1 mouse, were studied to investigate the pathogenicity of anticardiolipin antibodies (aCL). Four of 18 MoaCL were found to react with rabbit TM when examined using ELISA.These four MoaCL also reacted with synthetic peptide that included the epidermal growth factor-like (EGF-like) domain to human TM,a binding site for thrombin. The reaction with TM of these four MoaCL was inhibited by bovine thrombin. When the affinity for TM of the MoaCL was determined, the dissociation constants (Kd) ranged from 4.8 x 10-9 to 4.7 x 10-8 M.By contrast, examination of the affinity for CL gave values from 8.3 x 10-6 to 7.4 x 10-5 M.Thus, these MoaCL reacted to TM with a higher affinity than to CL.Moreover, these MoaCL also bound to TM on human umbilical vein endothelial cells (HUVEC) and down-regulated the expression level of TM on the surface of HUVEC,due to internalization of TM.The binding of thrombin to TM is known to initiate rapid protein C activation and complexes of activated protein C and protein S show anticoagulatory activity. Thus, present studies suggest that certain pathogenic aCL cross-react with TM and induce down-regulation of TM on endothelial cells, followed by induction of thrombosis.
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[Publications] Haruta, K., Kobayashi, S., Hirose, S., Horiai, A., Ohyanagi, M., Tanaka, M., Kawano, T., Shirai, T., Takasaki, Y., Hashimoto, H.: "Monoclonal anti-cardiolipin antibodies from New Zealand black x white F1 mice react to thrombomodulin." The Journal of Immunology. 160. 253-258 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Biyajima, S., Osada, T., Daidoji, H., Hisaoka, T., Sakakibara, Y., Tajima, J., Nakazawa, M., Kuroda, H., Kobayashi, S.: "Pulmonary hypertension and antiphospholipid antibody in a patient with Sjogren's syndrome." Internal Medicine. 33(12). 768-772 (1994)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Haruta, K., Kobayashi, S., Tanaka, M., Ohyanagi, M., Kobayashi, H., Hirose, S., Shirai, T., Hashimoto, H.: "Monoclonal anticardiolipin antibodies from NZB/WF1 mouse react to hrombomodulin." Arthritis Rheum. 37(9). (1994)
Description
「研究成果報告書概要(欧文)」より
