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Anti-adhesive effects of human soluble thrombomodulin and its domains
http://hdl.handle.net/10076/00018456
http://hdl.handle.net/10076/00018456e4405987-164e-429d-82d1-d3d38666d43a
名前 / ファイル | ライセンス | アクション |
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2019DM0710.pdf (557.7 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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公開日 | 2019-10-24 | |||||||||||
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言語 | en | |||||||||||
タイトル | Anti-adhesive effects of human soluble thrombomodulin and its domains | |||||||||||
言語 | ||||||||||||
言語 | eng | |||||||||||
キーワード | ||||||||||||
主題Scheme | Other | |||||||||||
主題 | Thrombomodulin | |||||||||||
キーワード | ||||||||||||
主題Scheme | Other | |||||||||||
主題 | b2 integrin | |||||||||||
キーワード | ||||||||||||
主題Scheme | Other | |||||||||||
主題 | Vascular endothelial cell | |||||||||||
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主題Scheme | Other | |||||||||||
主題 | Inflammation | |||||||||||
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主題Scheme | Other | |||||||||||
主題 | Sepsis | |||||||||||
資源タイプ | ||||||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
資源タイプ | doctoral thesis | |||||||||||
アクセス権 | ||||||||||||
アクセス権 | open access | |||||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
著者 |
長太, のどか
× 長太, のどか
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抄録 | ||||||||||||
内容記述タイプ | Abstract | |||||||||||
内容記述 | We reported previously that leukocyte b2 integrins (LFA-1 and Mac-1) bind to the serine/threonine-rich domain of thrombomodulin (TM) expressed on vascular endothelial cells (VECs). Recombinant human soluble TM (rhsTM, TMD123) has been approved as a therapeutic drug for septic disseminated intravascular coagulation. However, the roles of TMD123 on the adhesion of leukocyte integrins to VECs remain unclear. In the current study, we have revealed that an integrin-dependent binding between human peripheral blood mononuclear cells (PBMCs) and VECs was inhibited by TMD123. Next, using mutant proteins composed of isolated TM extracellular domains, we examined the structural characteristics responsible for the anti-adhesion properties of TMD123. Namely, we investigated whether the effects of the binding of TM and leukocytes was inhibited by the administration of TMD123. In fact, we confirmed that TMD123, TMD1, and TMD3 inhibited the binding of PBMCs to the immobilized recombinant proteins TMD123 and TMD3. These results indicate that TMD123 inhibited the adhesion of leukocytes to endothelial cells via b2 integrins and endothelial TM. Moreover, since TMD1 might bind to leukocytes via other adhesion receptors than integrins, TMD1 and TMD3 appear to inhibit leukocyte binding to TM on VECs via different mechanisms. In summary, TMD123 (rhsTM), TMD1 or TMD3 is a promising treatment option for sepsis that attenuates integrin-dependent binding of leukocytes to VECs, and may inhibit the undesirable adhesion and migration of leukocytes to VECs in sepsis. | |||||||||||
内容記述 | ||||||||||||
内容記述タイプ | Other | |||||||||||
内容記述 | 本文/Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu-city, Mie, 514-8507, Japan | |||||||||||
内容記述 | ||||||||||||
内容記述タイプ | Other | |||||||||||
内容記述 | 6p | |||||||||||
書誌情報 |
発行日 2019-07-17 |
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DOI | ||||||||||||
識別子タイプ | DOI | |||||||||||
関連識別子 | 10.1016/j.bbrc.2019.02.041 | |||||||||||
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内容記述タイプ | Other | |||||||||||
内容記述 | application/pdf | |||||||||||
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出版タイプ | VoR | |||||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
出版者 | ||||||||||||
出版者 | 三重大学 | |||||||||||
出版者(ヨミ) | ||||||||||||
ミエダイガク | ||||||||||||
学位名 | ||||||||||||
学位名 | 博士(医学) | |||||||||||
学位授与機関 | ||||||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||||
学位授与機関識別子 | 14101 | |||||||||||
学位授与機関名 | 三重大学 | |||||||||||
学位授与年月日 | ||||||||||||
学位授与年月日 | 2019-07-17 | |||||||||||
学位授与番号 | ||||||||||||
学位授与番号 | 甲医学第1966号 | |||||||||||
ノート | ||||||||||||
Biochemical and Biophysical Research Communications 511 (2019) 312-317に掲載 | ||||||||||||
資源タイプ(三重大) | ||||||||||||
Doctoral Dissertation / 博士論文 |