Table:
Location specific functions of HMGB1 in sepsis and trauma
| Cell type | Posttranslational modification | Intracellular | Extracellular | |
|---|---|---|---|---|
| Modification | Functions | |||
| Monocyte & Macrophage | Acetylation with NLS site | Nucleus to the cytoplasm translocation [12] | Induce autophagy preventing macrophage cell death from endotoxemia and bacterial infection by mediating [67] | 1. Induce cytokines and chemokine production [56,57] 2. Deliver LPS into the cytoplasm [25] 3. Induce pyroptosis [25,58] |
| Phosphorylation with NLS site | Nucleus to the cytoplasm translocation [14, 21] | |||
| Fully reduced, all thiol | Chemotaxis [41] Delivery of LPS into the cytoplasm [25] |
|||
| Disulfide | Inflammatory response [40,42–45] | |||
| Hepatocyte | Acetylation with NLS site | Nucleus to the cytoplasm translocation [18] | 1. Stabilize nucleus and mitochondria preventing cell death during liver ischemia and reperfusion [50] 2. Activate Aim2 inflammasome [46] |
|
| Phosphorylation with NLS site | Nucleus to the cytoplasm translocation [22] | |||
| Fully reduced, all thiol | Activate Aim2 inflammasome [46] | |||
| Neutrophil | Methylation at lysine 42 | Passive diffusion out of the nucleus [23] | 1. Inflammatory response [60] 2. NADPH oxidase dysfunction [61] 3. Stimulate neutrophil extracellular trap formation [62] |
|
| Vascular endothelial cells | 1. Inflammatory response [44,63] 2. Induce loss of endothelial integrity [66–68] |
|||
| Intestinal epithelia cells | Bind to beclin initiating autophagy [49] | Induce mucosal barrier dysfunction [70] | ||
| Platelet | Activate platelets in sepsis [71] | Activate platelet and thrombosis in trauma [72] | ||