Adhesion Molecules in Leukocytes and Their Reactivity - Adhesion Molecules - page 149

Table 1 Adhesion molecules expressed by leukocytes and their ligands

L-selectin Selectin ligands

Tetrasaccharide sialyl Lewis x (CD15s) binds all
selectins and it has been identii ed as a prototype
selectin ligand.
L-selectin recognizes heavily glycosylated
mucin-like proteins: glycosylation-dependent
cell adhesion molecule 1 (GlyCAM-1), high
endothelial venules ligand (sgp200), CD34, and
mucosal addressin (MadCAM-1) and P-selectin
glycoprotein ligand-1 (PSGL-1). MadCAM-1
is a dominant physiological ligand for the α 4 β 7 -
integrin and for L-selectin and has high degree
of homology with other immunoglobulin family
members, ICAM-1 and VCAM-1.

Expressed by majority of leukocytes. Expression
on the surface regulated by proteolytic cleavage
near the cell surface by disintegrins of ADAM
family. Cytoplasmic domain of L-selectin
consists of 17 amino acid residues and interacts:
α-actinin, calmodulin and members of ezrin/
radixin/moesin (ERM) family. Calmodulin
interacts with the cytoplasmatic tail of L-selectin
in resting leukocytes negatively regulating its
shedding. Activation of leukocytes leads to a
release of calmodulin from the cytoplasmatic
tail of L-selectin followed by the concomitant
shedding of L-selectin.

Integrins Integrin ligands

Membrane-bound heterodimeric glycoproteins
consisting of noncovalently associated α and
β subunits. In humans, 18 α subunits and 8
β subunits have been described giving rise to
24 integrin α/β dimers. Expression pattern
of heterodimers varies among dif erent cell
types. Integrins control leukocyte homing
to hematopoetic organs and also to sites of
inl ammation. h e binding of integrins to their
ligands is facilitating antigen recognition.

Intercellular adhesion molecules (ICAMs) are
surface glycoproteins and structurally belong to
the immunoglobulin (Ig) family and are ligands
for the β 2 -integrins. Expression of ICAMs is
ot en constitutive and spread between multiple
cell types. Some of ICAM subtypes (ICAM-2
and ICAM-3) appear only on lymphocytes and
monocytes, which led to the proposal of their role
in initiating immune responses.

Integrins are cell membrane heterodimeric glycoproteins consisting of
noncovalently associated subunits (Fig. 1) . In response to stimulation,

integrins signal through a conformation change of extracellular domains leading
to polymerization, clustering and exposure of dif erent binding epitopes. h e
extracellular domains of

α and β

-integrins are formed by series of globular
domains that incorporate genu, a folding point of extracellular domains. In the
bend position, the knee is folded, and the integrins assume a compact structure in
which the ligand binding site is close to the membrane. In the extend conformation
state of the integrin legs, the ligand-binding site is projected away from the
membrane and has limited availability for ligands (Fig. 2) . h is conformation
probably depicts most closely the conformation of integrins in circulation (Hynes
2002).
Neutrophils and eosinophils can be rapidly recruited to the sites of inl ammation.
In contrast, monocytes and natural killer cells migrate at low levels. T lymphocytes
are recruited to the inl ammation site selectively from the nearest lymph nodes.
Once arrived at their destination, leukocytes enter tissues through the vascular
endothelium. Leukocyte interaction with vascular endothelial cells involve multiple

α - and β