Selectines
DefinitionThis section has been translated automatically.
Group of carbohydrate-binding (lectin-like) adhesion molecules which in acute or chronic inflammation contribute decisively to the adhesion of leukocytes to the vascular endothelium and their chemotactic emigration into the inflamed tissue (see PRRs below).
ClassificationThis section has been translated automatically.
A distinction is made between:
- L-Selectin
- E-selectin
- P-selectin.
General informationThis section has been translated automatically.
Selectins initiate a complex cascade of adhesion events by locally concentrating flowing leukocytes from the capillary blood stream by mediating rolling deceleration along the vessel wall. This process occurs in a cascade of sequential molecular interactions.
First, selectins mediate "docking" and rolling of leukocytes on the endothelial surface. This leads to the slowing of leukocytes and allows contact with signaling substances on the endothelial surface, such as chemokines. These stimulate the activation of integrins on the leukocyte surface. Integrins then mediate the efficient binding of these cells to the endothelial surface.
Members of the immunoglobulin (Ig) superfamily act as ligands of integrins. The leukocytes, which are now stably adherent, are able to target and eventually actively migrate through the endothelial cell layer.
Of the three known selectins, one, L-selectin, is found on most leukocytes, whereas E-selectin is expressed exclusively by endothelial cells and P-selectin is found on endothelium and on platelets.
OccurrenceThis section has been translated automatically.
Leukocyte adhesion deficiency II (LAD II) is a genetic defect that leads to a primary immunodeficiency due to the absence of selectin ligands (recurrent severe infections with fever episodes, dramatic increase in leukocyte counts in the blood).
Note(s)This section has been translated automatically.
Due to their initial role in the cellular immune defence against inflammatory events, the selectins with their structural and functional elucidation became an extremely attractive target structure for pharmaceutical research in the 1990s. The idea of being able to influence pathological inflammatory processes such as rheumatoid arthritis or myocardial ischemia by modulating or blocking selectin binding at a very early and causal point seems very promising.