Helicobacter pylori lipopolysaccharide-mediated gastric and extragastric pathology.

Lipopolysaccharides (LPS) are a family of toxic phosphorylated glycolipids in the outer membrane of Gram-negative bacteria, including Helicobacter pylori, and are composed of a lipid moiety (termed lipid A), a core oligosaccharide, and a polymeric O-specific polysaccharide chain. Compared with LPS of other bacteria, H. pylori LPS and lipid A induce low immunological activities in a range of test systems. Nevertheless, these reduced levels of LPS-induced cytokines and toxic oxygen radicals can contribute, with those induced by bacterial proteins, to the H. pylori-associated inflammatory response. Whether the ability of H. pylori LPS to induce low production of both procoagulant activity and plasminogen activator inhibitor type 2 by human mononuclear cells contributes to localized inflammatory responses alone and, in addition, play a role in extragastric pathology remains an open question. The core oligosaccharide of H. pylori LPS, in part with a 25 kDa protein adhesin, mediates the binding of the bacterium to the host glycoprotein laminin, and hence interferes with gastric cell receptor-laminin interaction in the basement membrane. Also affecting mucosal integrity, the core sugars of certain H. pylori strains, particularly those associated with gastric ulceration, have been implicated in pepsinogen induction, but this is a strain-dependent phenomenon. Of particular interest, the O-chains of a large proportion of H. pylori strains mimic Lewis (Le) antigens. Although investigations have focussed on the role of these antigens in H. pylori-associated autoimmunity, which remains to be unequivocally established, other pathogenic consequences of Lewis mimicry are becoming apparent. Expression of Lewis antigens may be crucial for H. pylori colonization and adherence and, by aiding bacterial interaction with the gastric mucosa, thereby aid delivery of secreted products, and hence influence the inflammatory response.