Chemistry Reference
In-Depth Information
27.3
Selectins
Selectins are a family of three type 1 transmembrane glycoproteins. E-selectin
(CD62E) is expressed on the surface of endothelial cells and L-selectin (CD62L)
on the surface of leukocytes. P-selectin (CD62P), the largest selectin, is stored in
α
-granules of platelets and in Weibel-Palade bodies of platelets and endothelial
cells, and is transferred to the cell surface upon activation (for further description
of selectins, please see Figure 16.1h, Chapter 19 and Chapter 29). Selectins are
involved in capture, rolling and fi rst contacts of leukocytes to the vascular endo-
thelial cell layer. In addition to their function in leukocyte migration and adhesion
to the vascular endothelium during the course of infl ammatory processes, selec-
tins are also important adhesion molecules in the migration of naï ve lymphocytes
to lymphoid organs. In 1964, James Gowan and his colleagues at Oxford Univer-
sity discovered that lymphocytes migrate from the blood circulation into lymphoid
organs. This process was later termed ' homing ' [1] . L - Selectins of lymphocytes
interact with their carbohydrate ligands expressed on a distinct type of endothelial
cells within postcapillary venules in the cortex of lymph nodes.
These vessels are commonly named high endothelial venules (HEVs) because
of the characteristic form of their endothelial cells. Similar to the rolling adhesion
to vascular endothelium at infl ammatory sites, lymphocytes also form L- selectin -
mediated contacts with HEVs by tethering and rolling along the apical site of
HEVs. This interaction with HEVs of lymphoid organs is an important early step
during the process of T lymphocyte-dependent B lymphocyte activation. There-
fore, selectins have vital functions both for the innate immune system (leukocyte
traffi cking to infl ammatory sites) as well as for the adaptive immune response
(lymphocyte homing). Further features of L-selectin are in leukocyte-leukocyte
interactions during infl ammation and leukocyte-tumor cell interactions during
the formation of metastasis. The interaction of selectins on endothelial cells with
ligands on tumor cells is described in Chapter 28.1 .
27.4
Selectin Carbohydrate Ligands and Their Carrier Glycoproteins
Selectin-ligand interactions during various immune reactions are summarized in
Table 27.1. Three different structural features characterize selectin carbohydrate
ligands to varying degrees: fucosylation, sialylation and sulfation. Carriers for the
carbohydrate selectin ligands are surface-expressed glycoproteins of the mucin
type as described in more detail below (see also Figure 27.1 a) [2] .
Selectins belonging to the group of C-type lectins have a carbohydrate recogni-
tion domain (CRD) in their N-terminal domain (see Figure 16.1h and Chapter 19,
and also Chapter 29 ). Sialyl - Le
x
also fi ts well in the complex with the CRD of
CD62E. CD62E and CD62P have been shown to have a much higher affi nity for
sialyl - Le
x
(CD15s) than for Le
x
(CD15). Structural details of a series of selectin
