{"created":"2023-06-19T11:43:20.069576+00:00","id":12837,"links":{},"metadata":{"_buckets":{"deposit":"8071e9ae-ce28-4146-9870-025da4746b9d"},"_deposit":{"created_by":16,"id":"12837","owners":[16],"pid":{"revision_id":0,"type":"depid","value":"12837"},"status":"published"},"_oai":{"id":"oai:mie-u.repo.nii.ac.jp:00012837","sets":["334:608:618:1214"]},"author_link":[],"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-07-17","bibliographicIssueDateType":"Issued"}}]},"item_7_date_granted_59":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2019-07-17"}]},"item_7_degree_grantor_57":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"三重大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"14101","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_7_degree_name_56":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_7_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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.","subitem_description_type":"Abstract"}]},"item_7_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"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","subitem_description_type":"Other"},{"subitem_description":"6p","subitem_description_type":"Other"}]},"item_7_dissertation_number_60":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲医学第1966号"}]},"item_7_publisher_30":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"三重大学"}]},"item_7_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1016/j.bbrc.2019.02.041","subitem_relation_type_select":"DOI"}}]},"item_7_text_31":{"attribute_name":"出版者（ヨミ）","attribute_value_mlt":[{"subitem_text_value":"ミエダイガク"}]},"item_7_text_63":{"attribute_name":"ノート","attribute_value_mlt":[{"subitem_text_value":"Biochemical and Biophysical Research Communications 511 (2019) 312-317に掲載"}]},"item_7_text_65":{"attribute_name":"資源タイプ（三重大）","attribute_value_mlt":[{"subitem_text_value":"Doctoral Dissertation / 博士論文"}]},"item_7_version_type_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Nago, Nodoka","creatorNameLang":"en"},{"creatorName":"ナゴウ, ノドカ","creatorNameLang":"ja-Kana"},{"creatorName":"長太, のどか","creatorNameLang":"ja"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-10-24"}],"displaytype":"detail","filename":"2019DM0710.pdf","filesize":[{"value":"557.7 kB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"2019DM0710.pdf","objectType":"fulltext","url":"https://mie-u.repo.nii.ac.jp/record/12837/files/2019DM0710.pdf"},"version_id":"aab9e4cb-b735-48e8-af9c-a22422e23c34"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Thrombomodulin","subitem_subject_scheme":"Other"},{"subitem_subject":"b2 integrin","subitem_subject_scheme":"Other"},{"subitem_subject":"Vascular endothelial cell","subitem_subject_scheme":"Other"},{"subitem_subject":"Inflammation","subitem_subject_scheme":"Other"},{"subitem_subject":"Sepsis","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Anti-adhesive effects of human soluble thrombomodulin and its domains","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Anti-adhesive effects of human soluble thrombomodulin and its domains","subitem_title_language":"en"}]},"item_type_id":"7","owner":"16","path":["1214"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2019-10-24"},"publish_date":"2019-10-24","publish_status":"0","recid":"12837","relation_version_is_last":true,"title":["Anti-adhesive effects of human soluble thrombomodulin and its domains"],"weko_creator_id":"16","weko_shared_id":-1},"updated":"2023-10-26T00:44:39.017517+00:00"}