Gastric mucosal inflammatory responses to Helicobacter pylori.
Within the gastroduodenal mucosa Helicobacter pylori infection stimulates local production of a range of proinflammatory and immunoregulatory cytokines, neutrophil infiltration, specific T- and B-cell responses and the development of gastric lymphoid follicles. Following bacterial eradication this mucosal inflammatory response resolves. Infiltrating neutrophils are likely to be one of the major mediators of mucosal damage. Neutrophil activation, including reactive oxygen metabolite production and the release of myeloperoxidase, will be induced directly by bacterial factors and indirectly through products of complement activation, bioactive lipids and host-derived cytokines. Interleukin-8, and related peptides of the chemokine family secreted by gastric epithelial cells, are likely to be important host mediators inducing neutrophil migration to sites of infection. Epithelial IL-8 is upregulated by TNF-alpha and IL-1 and directly by H. pylori strains expressing the CagA phenotype. The extent of mucosal injury may reflect bacterial density, the variability of different strains of H. pylori to induce chemokine expression in epithelial cells and the oxidative burst in neutrophils. Recent evidence from in vivo and in vitro studies shows that CagA+ VacA+ strains of H. pylori are associated with enhanced inflammatory responses and mucosal damage. Defining the specific bacterial mediators of mucosal inflammation will be important in elucidating the role of H. pylori in the pathogenesis of gastroduodenal disease.
Crabtree
J E
JE
Division of Medicine, St James's University Hospital, Leeds, UK.
D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000276:immunology / Q000382:microbiology*; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D013045:Species Specificity
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D016209:Interleukin-8; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; D018664:Interleukin-12