Interaction between beta2 integrin and thrombomodulin effect to immunothrombosis

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K20386
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Mie University
• Principal Investigator: Kawamoto Eiji 三重大学, 医学部附属病院, 助教 (20577415)
• Research Collaborator: ITOU Asami 三重大学, 医学部附属病院, 助教 (80740448) ; IMAI Hiroshi 三重大学, 医学部附属病院, 教授 (00184804) ; OKAMOTO Takayuki 島根大学, 医学部, 准教授 (30378286) ; PARK Eun Jeong 三重大学, 大学院医学系研究科分子病態学, 准教授 (20644587) ; SHIMAOKA Motomu 三重大学, 大学院医学系研究科分子病態学, 教授 (40281133)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: beta2 integrin / thrombomodulin / anti inflammation / anti coagulation / 炎症と凝固のクロストーク / Immunothrombosis

Outline of Final Research Achievements

Immunothrombosis, the immune response of blood vessels caused by preventing the spread of bactearia, plays an important role in inflammation and coagulation for sepsis. Many researchers are going to investigate that coagulation factor, like APC and EPCR, binds to leukocyte, leading to immunothrombosis.　We have indicated that leukocyte LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin (TM). In fact, integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells, or immunothrombosis. Based on the results, we indicated here how the coagulation factor, TM on endothelial cell, is associated with leukocyte binding. First, we confirmed that the TNF -alpha induced inflammatory response downregulates TM expression on endothelial cells. Moreover we showed that pheripheral blood mononuclear cells (PBMCs) bind to human umbilical vein endothelial cell (HUVEC) dependent upon integrin activation.

Free Research Field

敗血症における炎症制御