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ABSTRACT
Liver ischemia reperfusion injury is mediated by a complex system of signaling cascades and inflammatory response resulting in organ damage. Selectins are a group of cell adhesion glycoproteins that play a key role in the initial immunological response. L-selectins, found on leukocytes, initiate the original adhesion and rolling phase of leukocyte extravasation upon liver sinusoidal endothelial cells (LSECs). P-selectins, found on platelets and tissue-specific endothelial cells, further increases leukocyte-endothelial adhesion and rolling. P-selectin-ligand binding also initiates intracellular signals that produce adhesion molecules to start firm adhesion and increase local chemokine production. L-selectin-ligand binding on the leukocytes increases adhesion molecule expression and chemokines, but also initiate changes in intracellular structural actin. E-selectin expression occurs with the presence of TNF-α and/or IL-1β. E-selectin-ligand binding decreases leukocyte rolling velocity and increases adhesion molecules. Together, these glycoproteins transition the leukocyte response from original margination and rolling to firm adhesion and eventually migration.
| ABBREVIATIONS | ||
| ADAP | = | adhesion and degranulation promoting adapter protein |
| ATP | = | adenosine triphosphate |
| Btk | = | Bruton tyrosine kinase |
| CD | = | cluster of differentiation |
| COPD | = | chronic obstructive pulmonary disease |
| DAMP | = | danger-associated molecular pattern |
| ERK | = | extracellular signal-regulated kinase |
| ERM | = | ezrin–radixin–moesin |
| E-selectin | = | endothelial selectin |
| ESL | = | endothelial selectin ligand |
| GM-CSF | = | granulocyte macrophage colony-stimulating factor |
| ICAM | = | intracellular adhesion molecule |
| IFN | = | interferon |
| IκB | = | inhibitor of kappa B |
| IL | = | interleukin |
| I/R | = | ischemia/reperfusion |
| LFA | = | lymphocyte function-associated antigen |
| LSEC | = | liver sinusoidal endothelial cell |
| L-selectin | = | lymphocyte selectin |
| JNK | = | janus kinase |
| MAPK | = | mitogen activated protein kinase |
| MIP | = | macrophage inflammatory protein |
| NF-κb | = | nuclear factor kappa-light-chain-enhancer of activated B cells |
| NOX | = | NADPH oxidase |
| PAMP | = | pathogen-associated molecular patterns |
| PKC | = | protein kinase C |
| P-Selectin | = | platelet selectin |
| PSGL | = | P-selectin glycoprotein ligand |
| ROS | = | reactive oxygen species |
| sL-selectin | = | soluble lymphocyte selectin |
| TNF | = | tumor necrosis factor |