Presence of terminal N-acetylgalactosamineβ1-4N-acetylglucosamine residues on O-linked oligosaccharides from gastric MUC5AC: Involvement in Helicobacter pylori colonization?

Abstract

Isolation of MUC5AC mucins from the gastric mucosa from two secretor individuals (one from normal mucosa from a patient with gastric cancer and one from a control) showed different abilities to bind and induce the proliferation of the Helicobacter pylori strain J99. Analysis of the released O-linked oligosaccharides by LC-MS from these individuals showed a very heterogeneous mixture of species from the cancer patient containing both neutral and sialylated structures, whereas the normal sample showed dominating neutral blood group H terminating structures as well as neutral structures containing the di-N-acetyllactosamine (lacdiNAc) unit GalNAcβ1-4GlcNAcβ1- on the C-6 branch of the reducing end GalNAc. The linkage configuration of these epitopes were determined using C-4-specific fragmentation for the GalNAcβ1-4GlcNAcβ1- glycosidic linkage, comparison of the MS(3) fragmentation with standards for linkage configuration and N-acetylhexosamine type as well as exoglycosidase treatment. It was also shown that the lacdiNAc epitope is present in both human and porcine gastric mucins, indicating that this is an epitope preserved between species. We hypothesize that the termination on gastric MUC5AC with lacdiNAc is in competition with complex glycosylation such as the Le(b) and H type 1 as well as complex sialylated structures. These are epitopes known to bind the H. pylori BabA and SabA adhesins.

Structural Diversity of Human Gastric Mucin Glycans

“…In agreement with previous studies (38,41), the core 2 O-glycans were the dominant structure in human gastric mucins. The interindividual heterogeneity of gastric O-glycans was mainly because of ABH and Lewis blood group epitopes.…”

“…3B, an extended core 1 like glycan was found to be capped with an ␣1,4-GlcNAc-like epitope ( 0,2 A 2 -H 2 O ions at m/z 304). The presence of LacdiNAc like structures on human gastric O-glycans was first described in our previous study based on O-glycan profiles from P10H and P5TA-AS (38). In this study, samples from additional 8 individuals were included.…”

Helicobacter pyloriBabA in adaptation for gastric colonization

“…The gastric mucin MUC5AC with N-acetylgalactosamine-β-1,4-N-acetylglucosamine residues on O-linked oligosaccharides from gastric MUC5AC has also been reported to act as receptor for BabA[68,69]. Most recent immunohistochemistry laden tissue profiling assay using mice model showed that the expression of Leb structure is a mucin α 1,2-fucosyltransferase (FUT2) enzyme dependent and consequently identified MUC5AC as the carrier molecule of the Leb structure[70].…”

Co-infections with liver fluke and Helicobacter species: A paradigm change in pathogenesis of opisthorchiasis and cholangiocarcinoma?

“…Toll-like receptor 4 (TLR4) is a known receptor for bacterial LPS [44]. The LabA adhesin specifically binds to GalNAcβ1-4GlcNAc motif, also known as N,N′-diacetyllactosediamine [lacdiNAc]), carried by MUC5AC mucins [45, 46]. However, orthologues of the human cell receptors and antigens have yet to be described from the epithelium of the gastrodermis of the gut of O. viverrini .…”