Chemistry Reference
In-Depth Information
mation by supporting tumor cell contact to the endothelium. Specifi c homing of
malignant lymphoma cells to bone marrow seems to be galectin mediated. A
prominent tumor - specifi c glycan, the Thomsen - Friedenreich ( TF ) antigen (CD176),
is a binding partner for galectin-3. Galectins-1 and -3 seem to have an additional
function in angiogenesis (Table 27.4). Exogenously added galectin- 3 induces tube
formation of vascular endothelial cells.
One major function of galectins in the immune system is the recognition of
microbial and parasitic glycoconjugates, which may then trigger further positive
or negative immune responses [8]. For example, galectins- 3 and - 9 recognize
surface lipophosphoglycans of
Leishmania major
and galectins- 1 and - 3 stimulate
oxidative burst in neutrophils as a cytotoxic anti-pathogenic mechanism. All
these functions depend on recognizing sugar-encoded information, especially
from spatially accessible branch ends of glycan antennae. In addition to selectins
and galectins, these sites are also targets for another lectin group, the siglecs (for
molecular display, see Figure 19.1 ).
27.6
Siglecs
The siglecs are a group of sialic acid- binding I - type (belonging to the immuno-
globulin supergene family) membrane-spanning lectins expressed not only in the
cells of the immune system, but also in other cell types and tissues, e.g., the
nervous system (Table 27.6). Siglecs can mediate heterotypic cell- cell interactions
by virtue of their sialic acid-binding capacity and may also be involved in
cis
-
cis
interaction between siglecs expressed on the cell surface and neighboring sialic
acid residues [9]. Although the structures and molecular prerequisites for sialic
acid binding in the N- terminal V - set immunoglobulin - like domains have been well
studied
in vitro
, the physiological role of most siglecs is still unclear. The best
functionally studied siglec is CD22. This is a B lymphocyte- specifi c surface
receptor, which, in contrast to most other siglecs, exclusively interacts with
2 - 6 -
sialylated glycans and participates in the fi ne regulation of antibody production of
activated B lymphocytes (Figure 27.3) [10]. Strikingly, within the hematopoietic
system, B lymphocytes carry the largest quantity of
α
2 - 6 - sialylated surface carbo-
hydrates as potential CD22 ligands, and the strongest binding of CD22 to
α
2 - 6 -
sialylated glycans is indeed between B cells. Interestingly, in the regulation of
fi rst - line - defense immunoglobulins, murine siglec -G seems to have a negative
regulatory impact on the production of so-called natural antibodies of B1- type B
lymphocytes.
While CD22 has a propensity towards
α
α
2 - 6 - linked sialoglycans, most other
siglecs tend to bind preferentially to
2 - 3 - sialylated glycans (Table 27.6 ). It is
striking that most siglecs can be found in cells of the myelomonocytic lineage of
the hematopoietic system and on NK cells, and that they are absent from T cells.
It is therefore most likely that siglecs play a role in the innate immune system and
also during infl ammatory reactions. However, this is still hypothetical. Of further
interest is the interaction of siglecs on various immune cells with sialic acids
α
