170
chapter 10
Heteropolysaccharides I: Glycoproteins and Glycolipids
O u te r d o m a in
I n n e r d o m a in
I—A-
I—A-
Tv.
Y"
P r o te in b a c k b o n e
A s p a r a g i n e —
T y p ic a l s e r u m g ly c o p r o te in
■ + H « - ''’ N e u r a m in id a s e
A-
A-
- • — Tv.
T"
;t — •
- A s p a r a g i n e -
A s ia lo g ly c o p r o te in
F I G U R E 1 0 -1 4
Oligosaccharide side chain of a serum glycoprotein. The removal of the
terminal sialic acid residue by neuraminidase exposes the penultimate
galactose residue. The resulting asialoglycoprotein is cleared from the
circulation by a galactose receptor-mediated process in the hepatocytes.
■ = Sialic acid, • = N-acetylglucosamine,
A
= galactose,
T = mannose.
cells depend on many other factors (e.g., inactivation of
enzymes and oxidation of sulfhydryl proteins). If desialy-
lation occurs normally as part of the physiological mech-
anism in clearing glycoproteins and cells of the circula-
tory system, the anatomical location of this process is not
known. Other clearance systems for glycoproteins have
been identified, e.g., one in the reticuloendothelial system
that terminates with mannose and N-acetylglucosamine.
Information of this type has potential application in tar-
geting biologically active molecules to a specific tissue
site. For example, mannose-terminated catalytically ac-
tive lysosomal enzymes can be targeted to reticuloen-
dothelial cells. Such targeting of lysosomal enzymes
could be useful in the treatment of lysosomal enzyme-
deficiency diseases. The same principle can be applied
to targeting drugs to specific tissue sites by coupling the
drugs to glycoproteins with the appropriate terminal sugar
residues.
and legs leading to paralysis. It is a self-limited au-
toimmune disease. Most GBS cases have resulted from
an antecedent, acute infection of bacterial or viral ori-
gin; in children GBS has also been identified following
vaccination.
One major cause of bacterial gastroenteritis is
Campy-
lobacter jejuni
and this infection also may be followed
by GBS. Some serotypes of
C. jejuni
possess liposac-
charides that contain terminal tetrasaccharides identical to
ganglioside GM1. Antibodies made in response to the bac-
terial infection also attack GM1 which is widely present
in the nervous system. The antibodies directed against the
GM1 epitope cause an immune-mediated destruction of
nerve fibers. Thus, the sharing of homologous epitopes
between bacterial liposaccharides and gangliosides is an
example of molecular mimicry, which causes disease. Host
factors may also influence a person’s susceptibility to
GBS. Plasma exchange and intravenous immunoglobu-
lin administration are used for immunomodulation in the
therapy of GBS.
Supplemental Readings and References
Extracellular Matrix
M. H. Ascarelli and J. C. Morrison: Use of fetal fibronectin in clinical prac-
tice.
O b stetrica l a n d G yn eco lo g ica l S u rvey
52(Suppl.), SI (1997).
R. O. Hynes: Integrins: Versatility, Modulation and Signalling in Cell
Adhesion.
C ell
69, 11 (1992).
K. A. Piez: History of extracellular matrix: A personal review.
M a trix B io lo g y
16,85(1997).
J. Labat-Robert, M. Bihari-Varga, and L. Robert: Extracellular Matrix.
F E E S
L etters
268, 386 (1990).
W. K. Stadelmann, A. G. Digens, and G. R. Tobin: Physiology and healing
dynamics of chronic cutaneous wounds.
A m erica n J o u rn a l o f Surgery
176(SuppI. 2A), 265 (1998).
W. K. Stadelmann, A. G. Digens, and G. R. Tobin: Impediments to wound
healing.
A m e rica n J o u rn a l o f S u rg ery
176(Suppl. 2A), 395 (1998).
10.5 Molecular Mimicry of Oligosaccharides
and Host Susceptibility
In the previous section we discussed the presence of
oligosaccharide and protein blood group substances that
cause susceptibility to certain pathogens. In this sec-
tion we discuss an infectious agent that contains a com-
mon antigenic epitope with the host and that elicits an-
tibodies that cause a disease.
Guillain—Barré syndrome
(GBS) is one such disease. GBS is an acute inflamma-
tory neuropathy with progressive weakness in both arms
Blood Group Antigens
P. Agre and J-P. Cartron: Molecular biology of Rh antigens.
B lo o d
78, 551
(1991).
C-H. Huang, P. Z. Liu, and J. G. Cheng: Molecular biology and genetics of
the Rh blood group system.
S em in a rs in H em a to lo g y
37, 150 (2000).
A. O. Pogo and A. Chaudhuri: The Duffy protein: a malarial and chemokine
receptor.
S em in a rs in H em a to lo g y
37, 122 (2000).
M. Rios and C. Bianco: The role of blood group antigens in infectious
disease.
S em in a rs in H em a to lo g y
37, 177 (2000).
M. J. Telen: Erythrocyte blood group antigens: Polymorphisms of function-
ally important molecules.
S em in a rs in H em a to lo g y
33, 302 (1996).
M. J. Telen: Red blood cell surface adhesion molecules: Their possible role
in normal human physiology and disease.
S em in a rs in H em a to lo g y
37,
130 (2000).
