Chemistry Reference
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4 Tissue and physio-pathological specific glycosylation
repertoire of mucins
Not only the pattern of O-glycans differs for a same mucin or different
mucins expressed on different organs and tissues but also the subsets of
O-glycans for a same mucin in a same tissue can be modified during
development or under pathological conditions. This highlights unique
roles for different glycan structures as well as unique regulation of glycan
synthesis in particular cells.
Recent analytical advances, such as mass spectrometry techniques, have
facilitated the identification of mucin O-glycans from a number of human
and animal tissues and secretions such as saliva,
62,63
lung,
64,65
stomach,
51,66
small intestine and colon,
7,44,50,67-70
bladder
71,72
and cervix.
73
In this review, we particularly focus on glycosylation of gastrointestinal and
airway mucins, which are the main mucins exposed to bacteria.
We summarize our current understanding of the expression and roles of
O-Glycosylation during development and physio-pathological states.
Over the last 30 years, a large body of work has been collected to
structurally characterize airway mucin O-glycans in healthy individuals
and in patients (mostly CF patients) suffering from bacterial infection.
Airway mucins contain a variety of sulphated, sialylated and fucosylated O-
glycans, generally of the core 1 and core 2 types but also including core 3
and core 4 types.
49,51,64,65,74-77
More than 250 O-glycans have been iden-
tified by mass spectrometry in mucins from CF and non-diseased patients.
The exact differences in glycosylation, which are associated with CF re-
main unclear, mainly due to the diculty of collecting sputum form
healthy individuals as they cannot easily expectorate. However, accumu-
lated data indicate an overall increase in sialylation and 6-sulfation
(GlcpNAc-6-sulfate and Galp-6-sulfate) in mucins from CF patients com-
pared to non-diseased donors. The overall modification in the level of
sulphated mucins is still controversial among the different studies.
51,65,78
The structural epitopes of oligosaccharides detected on CF sputummucins
are consistent with the presence of abundant high-a
nity ligands for
pathogenic bacteria including Pseudomonas aeruginosa,suchasLe
a
,Le
x
,
Le
y
,sLe
x
and other fucosylated, sialylated, and sulphated epitopes.
79
This
increased binding may then contribute to increased pulmonary infection
and biofilm development in CF patients. Remarkably, these O-glycans are
also ligands for inflammatory leukocytes that recognize sialylated, fuco-
sylated and sulphated oligosaccharides.
80
These data suggest that there is
inflammation/infection dependent glycosylation of epithelial secretions in
CF, which can even affect patients in their early childhood.
The gastric mucosa of healthy individuals is covered by more than 70
different oligosaccharides, mostly neutral and highly fucosylated.
65,81
Only
few sialylated glycans are identified and no sulphated glycans are
recovered. Almost all the gastric O-glycans are constructed on a tetra-
saccharide core 2 based structure: Fucp-(1
-
2)-b-Galp-(1
-
3)-[b-GlcpNAc-
(1
6)-]a-GalpNAc. The lower branch is never elongated except the presence
of blood group A or B antigens. The extreme heterogeneity of gastric mucin
glycosylation is mainly due to the elongation of the upper branch with
-
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