Biomedical Engineering Reference
In-Depth Information
L-Selectin
L-selectin is constitutively expressed on the microvilli of leukocytes. Cell surface
levels of L-selectin are regulated by metalloproteinase-dependent cleavage of the
extracellular domain following leukocyte activation (Smith 2008). h e intracellular
tail of L-selectin binds to calmodulin, and to the actin cytoskeletan via α-actinin
and the ezrin/radixin/moesin protein family. h e balance between these competing
intracellular interactions may inl uence the proteolytic cleavage of the extracellular
domain (Ivetic and Ridley 2004). h e extracellular domain of L-selectin binds
both PSGL-1 and glycoproteins found on specialized high endothelial venules of
peripheral lymphoid tissue (Smith 2008).
Selectin Functions
h e selectins act together to promote tethering and rolling of leukocytes along the
vascular endothelium. h is occurs under dynamic conditions, as blood l owing in
the capillaries exerts shear forces on the leukocytes and platelets as they interact
with each other and endothelial cells (McEver 2002, Smith 2008). At low shear
rates, leukocytes are unable to roll, but as shear rates increase past a threshold,
selectin-ligand bonds are strengthened, a phenomenon known as 'catch bonds'
(Smith 2008). When shear rates increase beyond an optimal level, bonds weaken
and shorten the lifetime of selectin-ligand binding. h ese interactions are called
'slip bonds' (Smith 2008). A combination of catch and slip bonds allows leukocytes
to roll along endothelia between 100 and 1000 times slower than the mean rate of
blood l ow, with rolling sustained by the formation of new and the dissociation of
old bonds (Smith 2008).
SUMMARY
• Cell adhesion receptors mediate cell communication and cell-cell and cell-
matrix interactions.
• Without cell adhesion molecules, there would be no multicellular
organisms.
• h e main groups of cell adhesion receptors are the Ig superfamily, integrins,
cadherins and selectins
• Cell-cell adhesion is mediated primarily by cadherins and is modulated by
members of the Ig superfamily.
• Integrins are critical for cell-matrix interactions.
• Selectins mediate leukocyte tethering and rolling in the blood
vasculature.
