@article{oai:hirosaki.repo.nii.ac.jp:00003616,
 author = {Maruyama, Ikuro and Ito, Takashi and Hashiguchi, Teruto},
 issue = {Supplement},
 journal = {弘前医学},
 month = {Nov},
 note = {application/pdf, Responses to stimuli in cellar level are diverse and such hierarchical as secretion of stored factors,
synthesis of lipid mediators and protein synthesis through genomic transcription. However, how can the cells
respond in the case of necrosis? Recently a characteristic intranuclear protein, high-mobility group box 1 protein
（HMGB1） is released from necrotic cells. The protein is an abundant nuclear protein with a dual function
both inside and outside the cells. In physiological state, HMGB1 is present in the nucleus, and binds to DNA,
playing a variety of crucial functions, including transcription and keeping the characteristic DNA architecture.
However, the protein is released to extracellular space from most of necrotic cells, activated macrophages and
dendritic cells. Out of the cells, HMGB1 acts as a signal of tissue damage and can promote infl ammation, immune
responses, and results tissue regeneration. During sepsis and/or disseminated intravascular coagulation （DIC）,
however, massive accumulation of HMGB1 in the systemic circulation will cause multiple organ failure （MOF）
and subsequent lethal outcome. Thus HMGB1 in the systemic circulation has been considered as a lethal
mediator of sepsis, and a promising therapeutic target for sepsis. Recently we identified that thrombomodulin
（TM）, a natural anticoagulant glycoprotein expressed on the surface of endothelial cells, plays an important
role in sequestering HMGB1. TM may prevent HMGB1 from reaching remote organs, thereby restricting
the spectrum of HMGB1 action in the site of injury. Here we review recent progress made in defining the
physiological and pathological roles of HMGB1 and therapeutic strategies aimed at blocking circulatory HMGB1., 弘前医学. 59(Suppl.), 2007, p.S1-S11},
 pages = {S1--S11},
 title = {Newly identifi ed message for rescue and repair from necrotic cell: Biology and clinical relevance of“endokine, HMGB1”},
 volume = {59},
 year = {2007}
}