Protein Glycosylation: Implications for In Vivo Functions and Therapeutic Applications - Advances in Biochemical Engineering Biotechnology - page 171

act as receptors for pathogens and toxins.Cell surface glycoconjugate containing
N -acetyl-9- O -acetylneuraminic acid is believed to be involved in the attachment
of influenza C virus [119].Again,sialic acid in glycophorin,a glycoprotein in the
membranes of red blood cells, has a role in the binding of viruses to receptors.
Removal of negative charge by chemical amidation blocks association of ence-
phalomyocarditis virus to receptors, suggesting a direct role for SA in attach-
ment [120].
Carbohydrate mediated cell-adhesion is involved in metastasis and can be
initiated by tissue injury or infection. One of the initial events in host response
to inflammation is the ordered migration of leukocytes to inflammatory sites,
initiated by relatively low affinity interactions that allow for leukocytes to roll
along the inner lining of blood vessels, called the endothelium. Finally, the rec-
ognition is mediated in most regulated manners by glycoprotein E-selectin
expressed on the surface of endothelial cells in response to inflammation, and a
glycan displayed on the surface of neutrophils occurs [121]. The adhesion pro-
cess is stimulated by signaling molecules (e.g. interleukin 1 and tumor necrosis
factor) or other inflammatory factors (e.g. toxins, lipopolysaccharides, leuko-
trines) that induce the production of E-selectin. Another glycoprotein, P-selec-
tin is expressed on thrombin activated endothelial cells. Passing leukocytes
adhere to these protruding selectins, as their carbohydrate coat contains com-
plementary ligands. The nature of carbohydrate ligands for the selectins
appear to be complex where Fuc and SA are critical functional components
[122]. Following this initial phase, tight adherence of leukocytes to the endo-
thelial cells takes place which involves protein-protein interactions mediated
by integrins on leukocytes and a protein ligand on endothelial cells. Finally,
leukocytes extravasate into the underlying tissue, where they play a key role in
host defense [122].
The lectin-carbohydrate recognition has also been implicated in the early
development and differentiation of cells. Neural cell adhesion molecules
(NCAM), are the cell surface glycoproteins which plays a key role in the devel-
opment of the nervous system [123]. NCAM, with polysialic acid (PSA) appear
during the early development and are believed to be involved in cellular adhe-
sion. The negatively charged PSA, more abundant in embryonic brain than
in adult brain, is implicated in reducing NCAM adhesive capability, and thus
in allowing increased neurite outgrowth and cell mobility.
3.6
Receptor Binding and Signal Transduction
Glycosylation adds to the heterogeneity and signaling functions of the cytoki-
nes, including the interferons, interleukins, colony stimulating factors [124].
However, the most well studied proteins in which direct participation of the
glycan moiety in their function including subunit assembly, receptor binding,
function and modulation of plasma half-life has been shown are the pituitary
hormones TSH, LH and FSH, and the placental hormone CG [125, 126]. These