Functional analysis of monocyte-lineage blood cells and control of damage-associated molecular patterns (DAMPs) under the whole-body responses to injury/illness

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H05009
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Keio University
• Principal Investigator: NAMIKI JUN 慶應義塾大学, 医学部(信濃町), 客員准教授 (20189195)
• Research Collaborator: SUZUKI Sayuri ; HAYASHIDA Kei ; SHIBUSAWA Takayuki ; TAMURA Tomoyoshi ; ISHIHAMA Yasushi
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 生体侵襲 / ヒストン / 敗血症 / 肝損傷

Outline of Final Research Achievements

Expression of HLA-DR temporary decreased in peripheral monocytes of patients with severe trauma, suggesting that a response reflecting the compensatory anti-inflammatory response syndrome that worsen the prognosis after trauma. Phosphorylation of Histone H3 was observed in monocytes of severe sepsis patients and may be an indicator for broken monocytes after the whole-body responses to injury/illness.
It is known that damage-associated molecular patterns (DAMPs) release into the bloodstream after the whole-body responses to injury/illness and worsen the prognosis. HMGB-1 and total Histone H3 related to poor prognosis in septic patients. Our study of liver injury model mice showed especially total Histone H3 may be a target molecule for control of DAMPs.

Free Research Field

救急医学

Academic Significance and Societal Importance of the Research Achievements

従来は全身反応を引き起こす分子として炎症性サイトカインなどの液性因子が注目されてきた。本研究では、体循環中の細胞成分とくに単球系細胞の反応と組織傷害関連物質（DAMPs）との関連に着目し、『組織傷害により体循環に放出されたDAMPs が単球を活性化して炎症性サイトカインの産生や組織因子の発現・放出、さらには単球の崩壊による更なるDAMPsの放出を引き起こして病態の急性転化をきたす』との仮説に基づき、重症生体侵襲の病態において重症度や転帰と関連するDAMPsや単球細胞の反応が新たな治療ターゲットとなる可能性が明らかになった。