Biomedical Engineering Reference
In-Depth Information
matrix adhesion, (2) cell-cell adhesion, and (3) cell-pathogen
adhesion. A large number of receptors, which contain either the
β
3
or
β
1
chain, bind a motif in proteins consisting of arginine, glycine, and
aspartic acid (RGD) [30]. Such motifs are found in many proteins in
the extracellular matrix, including collagens and fibronectin as well
as proteins of microbial origin. However, it should be noted that the
RGD motifs in proteins are so common that it is difficult to imagine
that the mere presence of this motif in a protein implies that the
protein is a functional significant integrin ligand. A similar aspect
has been addressed in analyses of the function of the family of
β
2
integrins. This family comprises the four receptors
α
L
β
2
(also known
as LFA-1 or CD11a/CD18),
α
M
β
2
(Mac-1, complement receptor 3,
CD11b/CD18),
α
X
β
2
(p150,95, complement receptor 4, or CD11c/
CD18), and
α
D
β
2
(CD11d/CD18), which are exclusively expressed
on leukocytes. These receptors support key functions of leukocytes,
including diapedesis through the endothelium and migration in the
extra cellular matrix. The function of integrin
α
L
β
2
is well established
and pertains mainly to binding to intercellular adhesion molecule
(ICAM)-1 during diapedesis and formation of contact with antigen
presenting cells.
α
L
β
2
binds a relatively limited number of ligands
that also include ICAM-2 and ICAM-3, which are structurally very
similar to ICAM-1 [31]. By contrast, the integrins
α
M
β
2
and
α
X
β
2
have
been reported to bind a large number of ligands with no structural
similarity and these include several proteins, endogenous and
microbial carbohydrate oligomers, and lipopolysaccaharide [32].
Furthermore, both in the case of
α
M
β
2
and
α
X
β
2
, procedures for
destroying higher-order protein structure appear to enhance binding
to the unfolded protein [33-35]. A rational for explaining these
findings was derived from studies of
α
X
β
2
where it appeared that the
receptor ligand-binding domain (the I domain) binds strongly to the
side chain of glutamic acid residues as well as to several other acid
compounds, including carboxylated alkyl chains [34]. In particular,
polyanions such as polyglutamic acid and heparin are strong ligands
for
α
X
β
2
[34, 36]. Interestingly, while
α
M
β
2
and
α
X
β
2
apparently share
many ligands, polyanions are not strong ligands for
α
M
β
2
. By contrast,
it appears that peptides carrying positively charged side chains bind
α
M
β
2
well, while this is not the case for
α
X
β
2
[37]. It is tempting to
speculate that the shared ability to recognize structurally decayed
macromolecular species but opposing requirements with regard
to the electrostatic charge of bound polymers reflects the need of
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