Biomedical Engineering Reference
In-Depth Information
h e selectins are a small family of lectin-like adhesion receptors comprising
three members, L-, E-, and P- selectin. Selectins mediate heterotypic cell-cell
interactions through calcium-dependent recognition of sialyated glycans. h e
best-dei ned physiological role of selectins is in leukocyte adherence to endothelial
cells and platelets during inl ammatory processes. h e expression and function of
selectins is tightly regulated so as to come into play only when leukocytes need
to stick to the vessel wall as part of normal immune system cellular trai cking or
during inl ammation. E-selectin is synthesized and expressed on endothelial cells in
response to inl ammatory cytokines such as tumor necrosis factor α or interleukin-1.
L-selectin is expressed constitutively on leukocytes, but its presentation at the cell
surface may be regulated. P-selectin (CD62P) is a membrane glycoprotein that is
rapidly mobilized to the surface of activated platelets and endothelial cells, where
it mediates leukocyte-platelet and leukocyte-vascular endothelial cell adhesion.
Moreover, P-selectin expression on activated platelets appears to be important for
the formation of large, stable platelet aggregates and for the amplii cation of the
leukocyte recruitment process and may prime monocytes for tissue factor and
cytokine upregulation.
It is known that CD62E (E-selectin) and CD62P (P-selectin) are upregulated
as part of the host response to injury or disease, where they play a key role in the
initial tether-roll phase of the homing of leukocytes to sites of inl ammation. h e
brain also utilizes the CD62 proteins, and they consequently of er an ideal, to date
underexploited, biomarker for brain disease diagnosis.
Human studies have shown increased selectin levels in ventricular CSF from
children with severe traumatic brain injury (Glasgow coma score < 8) (Whalen
et al
. 1998) and in patients with relapsing-remitting multiple sclerosis (Duran
et al
. 1999). Increased plasma levels of E-selectin have been shown to be associated
with AD (Zuliani
et al
. 2008). Selectins are also thought to contribute to tissue
injury in stroke. In multiple murine models of stroke, the use of selectin ligands
to block selectin function has reduced infarct size. For example, van Kasteren
and collaborators (van Kasteren
et al
. 2009) have demonstrated the application of
carbohydrate-functionalized nanoparticles to the direct detection of endothelial
markers E-/P-selectin (CD62E/CD62P) in acute inl ammation. h ese i rst
examples of glyconanoparticles visible by MRI display multiple copies of the
natural complex of glycan ligand with selectins. h eir resulting sensitivity and
binding selectivity has made possible sensitive detection of disease in mammals
with benei cial implications for treatment of an expanding patient population
suf ering from neurological disease.
Inl ammatory mechanisms and immune activation play a role not only in
neuro-degenerative conditions such as AD and vascular dementia, but also in
age-associated cognitive decline. For instance, Yaf e
et al
. (2003) followed 3,031
well-functioning subjects for 2 yr and reported that a high baseline level of
serum markers of inl ammation, most notably C-reactive protein and P-selectin,
