trans

230 TRYPANOSOMATID CARBOHYDRATES
polymorphisms have been identified among
the different strains (e.g. the presence of
galactofuranose rather than galactopyranose)
and only the G strain expresses oligosaccharides
containing a -galactofuranose residue.
The structure of the O-linked glycans from
mucins of a CL-Brener myotropic strain of
T. cruzi, the strain chosen for the Trypanosoma
genome project, has been recently reported.
The glycan structures are similar to those from
the reticulotropic Y strain. The differences in
structures of O-linked oligosaccharides from
mucins of various T. cruzi strains and developmental
stages may ultimately be related to distinctions
in infectivity and tissue tropism, or
to different growth conditions. The detailed
characterization of these differences may
eventually permit the identification of T. cruzi
ligands for receptors in the vertebrate host.
Both parasite and host-cell molecules are
believed to be involved in the complex process
of host-cell invasion. The surface coat of T. cruzi
seems to have a primarily protective function,
and the sialylation of the mucins provides
the parasite with the ability to survive in different
environments. Sialylation is proposed
to reduce the susceptibility of the parasite to
anti--galactose antibodies present in the
mammalian bloodstream. It has been proposed
that the heavily sialylated coat may also
provide a structural barrier to complementmediated
lysis, in escape from the endosomes,
in developmental stage transition, in promoting
adherence to the macrophage, in induction
of protective lytic antibodies, and in the
production of NO and cytokines.
The structures of the GPI anchors of the
mucins undergo modifications with parasite
differentiation. The epimastigote mucin
GPIs contain sn-1-alkyl-2-acylglycerol, while
over 70% of the metacyclic mucins contain
ceramide lipids; reviewed by Ferguson (1997,
1999; see Further Reading). Moreover, the
ceramide lipid species is found on LPPG
(lipopeptidophosphoglycan, see below), which
is expressed in large amounts on the epimastigote
surface. GPI anchors from the trypomastigote
stage of T. cruzi have been implicated
in the induction of NO, IL-12 and TNF-.
Trypomastigote GPIs contain unsaturated fatty
acids in the sn-2 position of the glycolipid
component. The observations that in noninfective
epimastigotes, the GPI-lipid anchor
of mucins is a 1-alkyl-2-acyl-PI, and that in
infective metacyclic forms the mucins possess
mostly ceramide-phosphoinositol suggest the
possibility that they may play a key role in the
release process during infection. Conceivably,
further clarification of this distinction might
lead to novel targets for chemotherapeutic
intervention.
Lipopeptidophosphoglycan
Lipopeptidophosphoglycan (LPPG) is the major
cell surface glycan of the T. cruzi epimastigote,
with about 1.5 10 7 copies per cell. The expression
of LPPG appears to be developmentally
regulated, as it is present in very low levels in
the stages that infect the mammalian host.
LPPG consists of a glycan linked to an inositolphosphoceramide
via a non-acetylated glucosamine
(Figure 10.2). The glycan structure
contains mannose, terminal galactofuranose
and 2-aminoethylphosphonate. The LPPG
fraction extracted from T. cruzi epimastigotes
contains three species that have slight variations
in the glycan structure, with respect to the
position of the Gal f . The major species (65%)
contains two terminal Gal f residues linked
1,3 to Man(1,2)Man. The lipid component
is an inositol phosphoceramide containing
mainly palmitoylsphinganine, palmitoylsphingosine
and lignoceroylsphinganine. LPPG
is considered a member of the GPI family
based on the presence of the Man(1,4)GlcN
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA