Abstract
Histidine-rich glycoprotein (HRG) is a plasma glycoprotein and exists in blood at a concentration of approximately 100 µg/ml. Although many previous reports already revealed that HRG has a wide range of activities against coagulation-fibrinolysis, immune and blood vascular system, we newly identified that HRG ameliorates a septic condition due to its inhibitory activity against immunothrombus formation starting from neutrophil-endothelial cell interaction. Additionally, we demonstrated that HRG regulates the translocation of HMGB1, damage-associated molecular pattern (DAMP) protein, from nuclei to cytosol and neutralizes the toxicity of heme, a kind of DAMP, and LPS, a kind of pathogen-associated molecular pattern (PAMP). Based on the above, HRG was thought to contribute the amelioration of a septic condition, caused by its regulatory activities against not only blood cell functions but DAMPs/PAMPs actions. Because DAMPs and PAMPs were associated with the exacerbation of not sepsis alone but a variety of inflammatory diseases, HRG, which regulates those reactions, has the potential of therapeutic drug for many kinds of diseases.
