Epithelial mucins and bacterial adhesion - Carbohydrate Chemistry: Chemical and Biological Approaches - page 607

(Gal3STs) and N-Acetyl-glucosamine 6-O-sulfotransferases (GlcNAc6STs)
catalyze the 3-O-sulfation of Gal residues and the 6-O-sulfation of GlcpNAc
residues on the acceptor oligosaccharide, respectively. cDNA encoding 3
different Gal3STs genes (GAL3ST2, 3 and 4) have been cloned and char-
acterized. They are active on type 1 and type 2 disaccharide units of
mucin carbohydrate 4)-b-

GlcpNAc structures, which are substrates for a1,3-fucosyltransferases
to generate the 3-sulfonato-Le x antigen (Table 3). Chandrasekaran
and co-workers have identified other preferential substrates for
these enzymes. Gal3ST-2 is active on the Globo H structure: b-Galp-(1

chains, generating (HO 3 S-3)-b-Galp-(1 -

-

3)-b-GalpNAc-(1 - 3)-a-Galp, Gal3ST-3 can use type 2 disaccharide

b-Galp-(1 - 4)-b-GlcpNAc of multi-antennary N-glycans and the b-Galp-

(1 4)-b-(HO 3 S-6)-GlcpNAc structure as substrates, whereas Gal3ST-4 acts

preferentially on mucin core 2. 53
GlcNAc-6-O-sulfation of mucin carbohydrate chains is achieved by a
family of GlcNAc-6-O-sulfotransferases. Two GlcNAc6STs, encoded by
CHST2 and CHST4 genes, are involved in 6-sulfonato-sLe x biosynthesis on
O-glycans. GlcNAc6ST-1, encoded by CHST2 gene, is ubiquitously
expressed, whereas GlcNAc6ST-2 (also called HEC-GlcNAc6ST) is mostly
expressed in high endothelial venules (HEVs). 54 Both enzymes are involved
in the biosynthesis of 6-sulfonato-sLe x epitopes on GlyCAM-1 O-glycans, a
mucin-like glycoprotein expressed on HEVs. The interactions between L-
selectin and 6-sulfonato-sLe x allow lymphocyte rolling on HEVs and their
homing to secondary lymphoid organs or to inflammation sites. A third
member of the GlcNAc6ST family, GlcNAc6ST-3, is mostly expressed in
intestine and colon, and is active on mucin O-glycans. 55 Finally, a Gal-
6-O-sulfotransferase has been cloned, involved in 6,6 0 -disulfonato-sLe x
synthesis

-

3)-]-b-
[HO 3 S-6]-GlcpNAc) on GlyCAM-1 and CD34, mucin-like glycoproteins
expressed on HEVs, and involved in L-selectin binding. 54 This enzyme is
possibly involved in the Gal-6-O-sulfation of secreted mucins.
Variations in sulfation of O-glycan chains have been described in several
pathologies, including cancers. Healthy colon epithelial cells express
3-sulfonato-Le a and 3-sulfonato-Le x epitopes, which are decreased in colon
cancer cells. 56 These observations are correlated to a decrease in GAL3ST2
sulfotransferase gene expression. 57 A general decrease in GlcNAc-6-sulfa-
tion and 6-sulfonato-sLe x expression has been associated with malignant
transformation of colon cells, with a concomitant increase in sLe x ex-
pression. A decreased expression of CHST6,encodingGlcNAc6ST3,the
main GlcNAc-6-O-sulfotransferase expressed in colon, has also been
observed during malignant transformation and could explain the balanced
expression of 6-sulfonato-sLe x and sLe x in healthy and cancer colon. 58
In cystic fibrosis, respiratory mucins secreted by patients are
over-sulphated. The 6-sulfonato-sLe x determinant is abundantly found in
respiratory mucins of CF patients 49 and is, together with sLe x , a prefer-
ential ligand for Pseudomonas aeruginosa, the major pathogen in the
cystic fibrosis lung. 59-61 The over-expression of these two determinants
may therefore be involved in the specificity and the development of the
lung infection in CF patients.

(a-Neup5Ac-(2 - 3)-b-[HO 3 S-6]-Galp-(1 - 4)-[a-Fucp-(1 -