Skip to main content
SpringerLink
Log in

Helicobacter pylori Infection in Gnotobiotic Piglets

A Model of Human Gastric Bacterial Disease

  • Chapter
Advances in Swine in Biomedical Research

Abstract

Helicobacter pylori, a gram negative microaerophilic urease positive and motile spiral shaped bacterium is the etiologic agent of human chronic superficial (active) gastritis. In humans, H. pylori is the primary cause of gastric ulcers and atrophic gastritis and a probable risk factor for the development of gastric carcinoma and gastric mucosa associated lymphoid tissue (MALT) lymphoma, presumably because of infection induced epithelial cell proliferation and increased mucosal exposure to orally ingested carcinogens in an acid neutral environment in the former and immunogenic overstimulation in the latter. The organism exhibits remarkable genomic variation among bacterial isolates, but genomic homogeneity within infected individuals suggesting that it is not subjected to selectional pressures by the host to ecological competition with other bacterial species. Normal gastric defenses which prevent colonization by most bacteria, do not hinder H. pylori and may restrict delivery of specific antibody or immune cells to the gastric lumen.

The gnotobiotic piglet, uniformly susceptible to oral infection from birth onward, is the most widely recognized infection and colonization model of human bacterial gastritis. Human origin virulent H. pylori, strain 26695, is adapted to optimal growth in piglets. This motile, urease positive isolate is CagA and cytotoxin (VacA) positive and achieves colonization levels (107 to 108 colony forming units/g mucosa) within 24 hr after oral inoculation. In addition, other bacterial strains (N6, WV99) but not all (Tx30a) colonize piglets; laboratory passed strains colonize poorly if at all. In pigs, as in humans, infection is restricted to the gastric microenvironment, persists in that location for at least 3 mo (pigs) or yr (humans) in spite of vigorous local and systemic immune responses. The microbe has a specific affinity for gastric mucus and adheres to gastric mucosal epithelia where it stimulates a multifocal or diffuse mononuclear lymphoplasmacytic inflammatory response with development of lymphoid follicles (pigs and children) and superficial neutrophilic infiltrates plus the lymphoplasmacytic lymphofollicular gastritis in adult humans. In piglets, the gastric inflammatory lesion can be modified to include the neutrophilic component by parenteral but not oral immunization with a killed autologous bacterin prior to infection. Gastric mucosal epithelial lesions, now recognized as diagnostic for H. pylori gastric infection, also occur in infected piglets. These include mucus depletion, epithelial cell vacuolation and degeneration, epithelial hyperplasia and necrosis with resultant gastric erosions and ulcerations.

The piglet model permits in vivo determination of putative bacterial virulence factors such as motility and/or presence of flagella, vacuolating cytotoxin (VacA) expression, urease enzyme presence and/or activity and infectivity of coccoid forms. In addition, a variety of conventional and experimental pharmaceuticals, antimicrobials and biologicals have been subjected to preclinical evaluation and efficacy in infected piglets. Both microbe related and host associated factors effect the pathogenesis of various components of the disease process. The relative importance of each alone or in combination can be determined in gnotobiotic piglets which possess a susceptible gastric microenvironment devoid of confounding variables such as concurrent commensal microbes, their products or effects on the host, diet, varying H. pylori burdens and strain differences, age, preexistent immunity and/or concurrent antimicrobial and antacid therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Marshall, B.J., and Warren, J.R., 1984, Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration, Lancet i: 1311–1314.

    Article  Google Scholar 

  2. Hazell, S.L., 1991, Urease and catalase as virulence factors of Helicobacter pylori, in: Helicobacter Pylori, (H. Menge, ed.), Springer-Verlag, Berlin, 3–14.

    Google Scholar 

  3. Labigne, A., Cussac, V., and Courcoux P., 1991, Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity, J. Bacteriol. 173:1920–1931.

    PubMed  CAS  Google Scholar 

  4. Marshall, D.G., Chua, A., Kneeling, P.W.N., Sullivan, D.J., Coleman, D.C., and Smyth, C.J., 1995, Molecular analysis of Helicobacter pylori populations in antral biopsies from individual patients using randomly amplified polymorphic DNA (RAPD) fingerprinting, FEMS, Immunol. Med. Microbiol. 10:3–4.

    Article  Google Scholar 

  5. Blaser, M.J., 1992, Hypotheses on the pathogenesis and natural history of Helicobacter pylori-induced inflammation, Gasteroenterol. 102:720–727.

    CAS  Google Scholar 

  6. Nwokolo, C.U., Bickley, J., Attard, A.R., Owen, R.J., Costas, M., and Fraser, I. A., 1992, Evidence of clonal variants of Helicobacter pylori in three generations of a duodenal ulcer disease family, Gut 133:1323–1327.

    Article  Google Scholar 

  7. Leunk, R.D., Johnson, P.T., David, B.C., Kraft, W.G., and Morgan, D.R., 1988, Cytotoxic activity in broth culture filtrates of Campylobacter pylori, J. Med. Microbiol. 26:93–99.

    Article  PubMed  CAS  Google Scholar 

  8. Cover, T.L., Puryear, W., Perez-Perez, G.I., and Blaser, M.J., 1991, Effect of urease on HeLa cell vacuolation induced by Helicobacter pylori cytotoxin, Infect. Immun. 59:1264–1270.

    PubMed  CAS  Google Scholar 

  9. Tummuru, M.K.R., Cover, T.L., and Blaser, M.J., 1993, Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: Evidence of linkage to cytotoxin production, Infect. Immun. 61:1799–1809.

    PubMed  CAS  Google Scholar 

  10. Stolte, M., and Eidt S., 1989, Lymphoid follicles in antral mucosa: Immune response to Campylobacter pylori? J. Clin. Pathol. 42:1269–1271.

    Article  PubMed  CAS  Google Scholar 

  11. Marshall, B.J., Armstrong, J.A., McGechie, D.B., and Glancy, R.J., 1985, Attempt to fulfill Koch’s postulates for pyloric Campylobacter, Med. J. Aust. 142:436–439.

    PubMed  CAS  Google Scholar 

  12. Morris, A.J., Ali, R., Nicholson, G.I., Perez-Perez, G.I., and Blaser, M.J., 1991, Long-term follow up of voluntary ingestion of Helicobacter pylori, Ann. Int. Med. 114:662–663.

    PubMed  CAS  Google Scholar 

  13. Krakowka, S., Morgan, D.R., Kraft, W.O., and Leunk, R., 1987, Establishment of gastric Campylobacter pylori infection in the neonatal piglet, Infect. Immun. 55:2789–2796.

    PubMed  CAS  Google Scholar 

  14. Lambert, J.R., Borromeo, M., Pinkard, K.J., Turner, H., Chapman, C.B., and Smith, M.L., 1987, Colonization of gnotobiotic piglets with Campylobacter pyloridis — An animal model, J. Inf. Dis. 155:1344.

    Article  CAS  Google Scholar 

  15. Prichard, P.J., and Yeomans, N.D., 1991, Helicobacter pylori and duodenal ulcer, J. Gastroent. Hepatol. 6:177–178.

    Article  CAS  Google Scholar 

  16. Peterson, W.L., 1991, Helicobacter pylori and peptic ulcer disease, N. Eng. J. Med. 324:1043–1047.

    Article  CAS  Google Scholar 

  17. Sipponen, P., 1991, Helicobacter pylori and chronic gastritis: An increased risk of peptic ulcer? A review, Scand. J. Gastroenterol. 26:6–10.

    Article  Google Scholar 

  18. Moss, S., and Calam, J., 1992, Helicobacter pylori and peptic ulcers: The present position, Gut 33:289–292.

    Article  PubMed  CAS  Google Scholar 

  19. Oderda, G., Vaira, D., Ainley, C., Holton, J., Osborn, J., Altare, F., and Ansaldi, N., 1992, Eighteen month follow up of Helicobacter pylori positive children treated with amoxycillin and tinidazole, Gut 33:1328–1330.

    Article  PubMed  CAS  Google Scholar 

  20. Forbes, G.M., Glaser, M.E., Cullen, D.J.E., Warren, J.R., Christianses, K.J., Marshall, B.J., and Collins, B.J., 1994, Duodenal ulcer treated with Helicobacter pylori eradication: Seven-year follow-up, Lancet 343:258–260.

    Article  PubMed  CAS  Google Scholar 

  21. Sipponen, P., and Hyvarinen, H., 1993, Role of Helicobacter pylori in the pathogenesis of gastritis, peptic ulcer and gastric cancer, Scand. J. Gastroenterol 28(Suppl 196):3–6.

    Article  Google Scholar 

  22. Nomura, A., Stemmermann, G.N., Chyou, P.-H., Kato, I., Perez-Perez, G.F., and Blaser, M.J., 1991, Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii, N. Engl. J. Med. 325:1132–1136.

    Article  PubMed  CAS  Google Scholar 

  23. Parsonnet, J., Vandersteen, D., Goates, J., Sibley, R.K., Pritikin, J., and Chang, Y., 1991, Helicobacter pylori infection in intestinal and diffuse-type gastric adenocarcinomas, J. Natl. Cane. Inst. 83:640–643.

    Article  CAS  Google Scholar 

  24. Forman, D., Newell, D.G., Fullerton, F., Yarnell, J.W.G., Stacey, A.R., Wald, N., and Silas, F., 1991, Association between infection with Helicobacter pylori and risk of gastric cancer: Evidence from a prospective investigation, Br. Med. J. 302:1302–1305.

    Article  CAS  Google Scholar 

  25. Sipponen, P., 1992, Helicobacter pylori infection — A common worldwide environmental risk factor for gastric cancer? Endos. 24:424–426.

    Article  CAS  Google Scholar 

  26. Hussell, T., Isaacson, P.G., Crabtree, J.E., Spencer, J., 1993, The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori, Lancet 342:7571–7574.

    Article  Google Scholar 

  27. Rodriguez, L.V., Hansen, S., Gelb, A., Friedman, G., Warnke, R.A., Jellum, E., and Parsonnet, J., 1993, Helicobacter pylori and gastric lymphoma: A nested case-control study, Acta Gastroenterol. Belgium 56(suppl):47.

    Google Scholar 

  28. Eidt, S., Stolte, M., and Fischer, R., 1994, Helicobacter pylori gastritis and primary gastric non-Hodgkins lymphomas, J. Clin. Pathol. 47:436–439.

    Article  PubMed  CAS  Google Scholar 

  29. Fox, J.G., Cabot, E.B., Taylor, N.S., and Laraway, R., 1988, Gastric colonization of Campylobacter pylori subsp. mustelae in ferrets, Infect. Immun. 56:2994–2996.

    PubMed  CAS  Google Scholar 

  30. Lee, A., Hazell, S.L., O’Rourke, J., and Kouprach, S., 1988, Isolation of a spiral-shaped bacterium from the cat stomach, Infect. Immun. 56:2843–2850.

    PubMed  CAS  Google Scholar 

  31. Eaton, K.A., Radin, M.J., Kramer, L., Wack, R., Sherding, R., Krakowka, S., and Morgan, D.R., 1993, Epizootic gastritis in cheetahs associated with gastric spiral bacilli, Vet. Pathol. 30:55–63.

    Article  PubMed  CAS  Google Scholar 

  32. Eaton, K.A., Radin, M.J., Kramer, L., Wack, R., Sherding, R., Krakowka, S., and Morgan, D. R., 1991, Gastric spiral bacilli in captive cheetahs, Scand. J. Gastroenterol. 26:38–42.

    Article  Google Scholar 

  33. Euler, A.R., Zarenko, G.E., Moe, J.B., Ulrich, R.G., and Yagi, Y., 1990, Evaluation of two monkey species (Macaca mulatta and Macaca fascicularis) as possible models for human Helicobacter pylori disease, J. Clin. Microb. 28:2285–2290.

    CAS  Google Scholar 

  34. McNulty, C.A.M., Dent, J.C., Curry, A., Uff, J.S., Ford, G.A., Gear, G.W.L., and Wilkinson, S.P., 1989, New spiral bacterium in gastric mucosa, J. Clin. Pathol. 42:585–591.

    Article  PubMed  CAS  Google Scholar 

  35. Reed, K.D., and Berridge, B.R., 1988, Campylobacter-like organisms in the gastric mucosa of Rhesus monkeys, Lab. Anim. Sci. 38:329–331.

    PubMed  CAS  Google Scholar 

  36. Henry, G.A., Long, P.H., Barns, J.L., and Charbonneau, D.L., 1987, Gastric spirillosis in Beagles, Am. J. Vet. Res. 48:831–836.

    PubMed  CAS  Google Scholar 

  37. Mendes, E.N., Queroz, D.M.M., Rocha, G.A., Moura, S.B., Leite, V.H.R., and Fonseca, M.E.F., 1990, Ultrastructure of a spiral micro-organism from pig gastric mucosa (“Gastrospirillum hominis”), J. Med. Microbiol. 33:61–66.

    Article  PubMed  CAS  Google Scholar 

  38. Fox, J.G., Dewhirst, F.E., Paster, B.J., Yan, L., Taylor, N.S. Collins, M.J., Gorelick, P.L., and Ward, J.M., 1994, Helicobacter hepaticus sp. nov., a microaerophilic bacterium isolated from livers and intestinal mucosal scrapings from mice, J. Clin. Microbiol. 32:1238–1245.

    PubMed  CAS  Google Scholar 

  39. Fox, J.G., Yan, L.L., Dewhirst, F.E., Paster, B.J., Shames, B., Murphy, J.C., Hayward, A., Belcher, J.C., and Mendes, E.N., 1995, Helicobacter bilis sp nov, a novel Helicobacter species isolated from bile, livers, and intestines of aged, inbred mice, J. Clin. Microbiol. 33:225–454.

    Google Scholar 

  40. Goodwin, C.S., Armstrong, J.A., and Marshall, B.J., 1986, Campylobacter pyloridis, gastritis and peptic ulceration, J. Clin. Pathol. 39:353–365.

    Article  PubMed  CAS  Google Scholar 

  41. Cantovna, M.T., and Balish, E., 1990, Inability of human clinical strains of Helicobacter pylori to colonize the ailmentary tract of germfree rodents, Can. J. Microbiol. 36:237–241.

    Article  Google Scholar 

  42. Handt, L.K., Fox, J.G., Dewhirst, F.E., Fraser, G.J., Paster, B.J., Yan, L.L., Rozmiarek, H., Rufo, R., and Stalis, I.H., 1994, Helicobacter pylori isolated from the domestic cat: Public health implications, Infect. Immun. 62:2367–2374.

    PubMed  CAS  Google Scholar 

  43. Marchetti, M.B., Arico, D., Burroni, N., Figura, R., Rappouli, R., and Ghira, P., 1995, Development of a mouse model of Helicobacter pylori infection that mimics human disease, Science 267:1655–1658.

    Article  PubMed  CAS  Google Scholar 

  44. Radin, M.J., Eaton, K.A., Krakowka, S., Morgan, D.R., Lee, A., Otto, G., and Fox, J.G., 1990, Campylobacter pylori gastric infection in gnotobiotic Beagle dogs, Infect.Immun. 58:2606–2612.

    PubMed  CAS  Google Scholar 

  45. Baskerville, A. and Newell, D.G., 1988, Naturally occurring chronic gastritis and C. pylori infection in the Rhesus monkey: A potential model for gastritis in man, Gut 29:465–472.

    Article  PubMed  CAS  Google Scholar 

  46. Dubois, A., Fiala, N., Heman-Ackah, L.M., Drazek, E.S., Tarnawski, A., Fishbein, W.N., Perez-Perez, G.I., and Blaser, M.J., 1994, Natural gastric infection with Helicobacter pylori in monkeys: A model for spiral bacteria infection in humans, Gasterenterol. 106:1405–1417.

    CAS  Google Scholar 

  47. Engstrand, L., Gustavsson, S., Jorgensen, A., Schwan, A., and Scheynius, A., 1990, Inoculation of barrier born pigs with Helicobacter pylori: A useful animal model for gastritis type B, Infect. Immun. 58:1763–1768.

    PubMed  CAS  Google Scholar 

  48. Engstrand, L., Rosberg, K., Hubinette, R., Berglindh, T., Rolfsen, W., and Gustavsson, S., 1992, Topographic mapping of Helicobacter pylori colonization in long-term-infected pigs, Infect. Immun. 60:653–656.

    PubMed  CAS  Google Scholar 

  49. Akopyants, N.S., Eaton, K.A., and Berg, D.E., 1994, Adaptive mutation and cocolonization during Helicobacter pylori infection of gnotobiotic piglets. Infect Immun. 63:116–121.

    Google Scholar 

  50. Sobala, G.M., Crabtree, J.E., Dixon, M.F., Schorah, C.J., Taylor, J.D., Rathbone, B.J., Heatley, R.V., and Axon, A.T.R., 1991, Acute Helicobacter pylori infection: Clinical features, local and systemic response. Gastric mucosal histology and gastric juice ascorbic acid concentrations, Gut 32:1415–1418.

    Article  PubMed  CAS  Google Scholar 

  51. Green, W.B., Eaton, K.A., and Krakowka, S., 1995, Tissue distribution of specific immunoglobulin synthesis in the gnotobiotic piglet model of H. pylori: infection. Am. of Gastroenterol. 89(217):51339.

    Google Scholar 

  52. Taylor, D.N., and Blaser, M.J., 1991, The epidemiology of Helicobacter pylori infection, Epidem. Rev. 13:42–59.

    CAS  Google Scholar 

  53. Hutter, C., and Poulter, L.W., 1992, The balance of macrophage subsets may be customised at mucosal surfaces, FEMS Microbiol. Immunol. 105:309–316.

    Article  Google Scholar 

  54. Eaton, K.A., Morgan, D.R., and Krakowka, S., 1989, Campylobacter pylori virulence factors in gnotobiotic piglets, Infect. Immun. 57:1119–1125.

    PubMed  CAS  Google Scholar 

  55. Eaton, K.A., Morgan, D.R., and Krakowka, S., 1992, Motility as a factor in the colonization of gnotobiotic piglets by Helicobacter pylori, J. Med. Micro. 37:123–127.

    Article  CAS  Google Scholar 

  56. Eaton, K. A, and Krakowka, S., 1994, Effect of gastric pH on urease-dependent colonization of gnotobiotic piglets by Helicobacter pylori, Infect. Immun. 62:3604–3607.

    PubMed  CAS  Google Scholar 

  57. Eaton, K.A., and Krakowka, S., 1991, Essential role of urease in the pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets, Infect. Immun. 59:2470–2475.

    PubMed  CAS  Google Scholar 

  58. Eaton, K.A., Morgan, D.R., and Krakowka, S., 1992, Motility as a factor in the colonization of gnotobiotic piglets by Helicobacter pylori, J. Med. Micro. 37:487–494.

    Article  Google Scholar 

  59. Eaton, K.A., Catrenich, C.A., Makin. K.M., and Krakowka, S., 1995, Virulence of coccoid and bacillary forms of Helicobacter pylori in gnotobiotic piglets, J. Inf. Dis. 171:459–462.

    Article  CAS  Google Scholar 

  60. Green, W.B., Eaton, K.A., and Krakowka, S., 1996, Porcine gastric mucosa associated lymphoid tissue (MALT): Stimulation by gastric infection with Helicobacter pylori, Vet. Immun. Immunopathol. In Press.

    Google Scholar 

  61. Krakowka, S., Ringler, S., Eaton, K.A., Green, W.B., and Leunk, R., 1996, Analysis of the gastric inflmmatory response in gnotobiotic piglets infected with Helicobacter pylori, Vet. Immun. Immunopathol. 52: 159–173.

    Article  CAS  Google Scholar 

  62. Eaton, K.A., Morgan, D.R., and Krakowka, S., 1990, Persistence of Helicobacter pylori in conventionalized piglets, J. Inf. Dis. 161:1222–1301.

    Article  Google Scholar 

  63. Krakowka, S., Eaton, K., and Morgan, D.R., 1991, Campylobacter pylori gastritis in gnotobiotic piglets: Persistence of gastric infection after conventionalization, in: Campylobacter, (G.M. Ruiz-Palacios, E. Calva, and B.R. Ruiz-Palacios, eds.), pp. 350–353.

    Google Scholar 

  64. Krakowka, S., Eaton, K.A., and Morgan, D.R., 1991, Gastritis induced by Helicobacter pylori in gnotobiotic piglets, Rev. Inf. Dis. 13:S681–685.

    Article  Google Scholar 

  65. Bull, D.M., and Bookman, M.A., 1977, Isolation and functional characterization of human intestinal mucosal lymphoid cells, J. Clin. Invest. 59:966–974.

    Article  PubMed  CAS  Google Scholar 

  66. Gibson-D’Ambrosio, R.E., Samuel, M. and D’Ambrosio, S.M., 1986, A method for isolating large numbers of viable disaggregated cells from various human tissues for cell culture establishment, In Vitro Cell. Devel. Biol. 22:529–534.

    Article  CAS  Google Scholar 

  67. Wilson, A.D., Stokes, C.R., and Bourne, F.J., 1986, Responses of intraepithelial lymphocyte to T-cell mitogens: A comparison between murine and porcine responses, Immunol. 58:621–625.

    CAS  Google Scholar 

  68. Krakowka, S., Eaton, K.A., and Rings, D.M., 1995, Occurence of gastric ulcers in gnotobiotic piglets colonized by Helicobacter pylori, Infect. Immun. 63:2352–2355.

    PubMed  CAS  Google Scholar 

  69. Owen, D.A., 1986, Normal histology of the stomach, Am. J. Surg. Pathol. 10:48–61.

    Article  PubMed  CAS  Google Scholar 

  70. Genta, R.M., Lew, G.M., and Graham, D.Y., 1993, Changes in the gastric mucosa following eradication of Helicobacter pylori, Mod. Pathol. 60:281–289.

    Google Scholar 

  71. Mooney, C., Keenan, J., Munster, D., Wilson, I., Allaedyce, R., Bagshaw, P., Chapman, B., and Chadwich, V., 1991, Neutrophil activation by Helicobacter pylori, Gut 32:853–857.

    Article  PubMed  CAS  Google Scholar 

  72. Krakowka, S., Morgan, D.R., Eaton, L.A., and Radin, M.J., 1991, Animal models of Camplylobacter pylori gastritis, in: Helicobacter pylori, (H. Menge, M. Gregor, G.N.J. Tytgat, B.J. Marshall, and C.A.M. McNulty, eds.), Springer-Verlag, Berlin, pp. 74–82.

    Google Scholar 

  73. Eaton, K.A., and Krakowka, S., 1992, Chronic active gastritis due to Helicobacter pylori immunized gnotobiotic giglets, Gastroenterol. 103:1580–1586.

    CAS  Google Scholar 

  74. Crabtree, J.E., Covacci, A., Farmery, S.M., Xaing, Z., Tompkins, D.S.S., Perry, S., Lindley, I.J.D. and Rappuoli, R.R., 1995, Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype, J. Clin. Pathol. 48:41–45.

    Article  PubMed  CAS  Google Scholar 

  75. Rudmann, D.G., Eaton, K.A., and Krakowka, S., 1992, Ultrastructural study of Helicobacter pylori adherence properties in gnotobiotic piglets, Infect. Immun. 60:2121–2124.

    PubMed  CAS  Google Scholar 

  76. Gorczyca, W., Tuziak, T., Krakm, A., Melamed, M.R., and Darzynkiewicz, Z., 1994, Detection of apoptosis-associated DNA strand breaks in fine-needle aspiration biopsies by in situ end labeling of fragmented DNA, Cytometry 15:169–175.

    Article  PubMed  CAS  Google Scholar 

  77. Marotta, R.B., and Floch, M.H., 1991, Diet and nutrition in ulcer disease, Med. Clin, of N. Amer. 75:967–979.

    CAS  Google Scholar 

  78. Mertz, H.R., and Walsh, J.H., 1991, Peptic ulcer pathophysiology, Med. Clin. N. Am. 75:799–814.

    PubMed  CAS  Google Scholar 

  79. Friedman, G.D., Siegelaub, A.B., and Seltzer, C.C., 1974, Cigarettes, alcohol, coffee and peptic ulcer, N. Eng. J. Med. 290:469–473.

    Article  CAS  Google Scholar 

  80. Krakowka, S., Eaton, K.A., and Morgan, D.R., 1991, Gastritis induced by Helicobacter pylori in gnotobiotic piglets, Rev. Inf. Disease 13:S681–S685.

    Article  Google Scholar 

  81. Dixon, M., Wyatt, J., Burke, D., and Rathbone, B., 1988, Lymphocytic gastritis-relationship to Campylobacter pylori infection, J. Pathol. 154:125–132.

    Article  PubMed  CAS  Google Scholar 

  82. Dixon, M.F., 1994, Pathophysiology of Helicobacter pylori infection, Scand J. Gastroenterol. 29(Suppl 201):7–10.

    Article  Google Scholar 

  83. Nagata, S., and Golstein, P., 1995, The fas death factor, Science 67:1449–1445.

    Article  Google Scholar 

  84. Bertram, T., Krakowka, S., and Morgan, D., 1991, Gastritis associated with infection by Helicobacter pylori: Comparative pathology in humans and swine, Rev. Infect. Dis. 13:S714–722.

    Article  PubMed  Google Scholar 

  85. Valnes, K., Brandtzaeg, P., Elgjo, K., and Stave, R., 1986, Quantitative distribution of immunoglobulin-producing cells in gastric mucosa: Relation to chronic gastritis and glandular atrophy, Gut 27:505–514.

    Article  PubMed  CAS  Google Scholar 

  86. Mathews, J.B., and Garner, A., 1991, Review article: Stomach wars — a mucosal defense initative, Ailment. Pharmacol. Therap. 5:1311–1314.

    Google Scholar 

  87. Pruul, H., Lee, P.C., Goodwin, C.S., and Macdonald, P.J., 1987, Interaction of Campylobacter pyloridis with human immune defense mechanisms, J. Med. Microbiol. 23:233–238.

    Article  PubMed  CAS  Google Scholar 

  88. Mai, U., Perez-Perez, G., Allen, J., Wahl, S., Blaser, M., and Smith, P., 1992, Surface proteins from Helicobacter pylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa, J. Exptl.Med. 175:517–525.

    Article  CAS  Google Scholar 

  89. Pavila, P., Hume, D.A., Van De Pol, E., and Doe, W.F., 1993, Dendritic cells, the major antigen-presenting cells of the colonic lamina propria, Immunol. 78:132–141.

    Google Scholar 

  90. Blaser, M., 1992, Hypotheses on the pathogenesis and natural history of Helicobacter pylori-induced inflammation, Gastroenterol. 102:720–727.

    CAS  Google Scholar 

  91. Buck, G., 1990, Campylobacter pylori and gastroduodenal disease, Clin. Microbiol. Rev. 3:1–12.

    PubMed  CAS  Google Scholar 

  92. Madan, E., Kemp, J., Westblom, T.U., Chaffin, C., and Foster, A., 1990, Histologic characteristics of Campylobacter pylori (Helicobacter pylori) mediated gastritis, Ann. Clin. Lab. Sci. 20:329–336.

    PubMed  CAS  Google Scholar 

  93. Nielsen, H., and Andersen, L., 1992, Chemotactic activity of Helicobacter pylori sonicate for human polymorphonuclear leucocytes and monocytes, Gut 33:738–742.

    Article  PubMed  CAS  Google Scholar 

  94. Reymunde, A., Deren, M.D., Nachamkin, I., Oppenheim, D., and Weinbaum, G., 1993, Production of chemoattractant by Helicobacter pylori, Digest. Dis. Sci. 38:1697–1701.

    Article  PubMed  CAS  Google Scholar 

  95. Rautelin, H., Blomberg, B., Fredlund, H., Jarnerot, G., and Danielsson, D., 1993, Incidence of Helicobacter pylori activating neutrophils in patients with peptic ulcer disease, Gut 34:599–603.

    Article  PubMed  CAS  Google Scholar 

  96. Wallace, J.L., Keenan, G.M., and Granger, N., 1990, Gastric ulceration induced by non-steroidal anti-inflammatory drugs is a neutrophil-dependent process, Am. J. Physiol. 259:462–467.

    Google Scholar 

  97. Norgaard, A., Andersen, L.P., and Nielson, N.D.H., 1995, Neutrophil degranulation by H. pylori, Gut 36:354–357.

    Article  Google Scholar 

  98. Moutiala, A., Helander, L., Pyhala, L., Kosunen, T., and Moran, A., 1992, Low biological activity of Helicobacter pylori liposaccharide, Infect. Immun. 60; 1714–1716.

    Google Scholar 

  99. MacDonald, T.T., and Spencer, J., 1990, The role of activated T cells in transformed intestinal mucosa, Digest. 46:290–296.

    Article  Google Scholar 

  100. Crabtree, J.E., Peichl, P., Wyatt, J.I., Stachl, U., and Lindley, I.J.D., 1993, Gastric interleukin-8 and IgA autoantibodies in Helicobacter pylori infection, Scand. J. Immunol. 37:65–70.

    Article  PubMed  CAS  Google Scholar 

  101. Davies, G.R., and Crabtree, J.E., 1994, Helicobacter pylori: Trick or treat? J. Roy. Soc. Med. 87:436–439.

    PubMed  CAS  Google Scholar 

  102. Fan, X.G., Chua, A., Fan, X.J., and Keeling, P.W.N., 1995, Increased gastric production of interleukin-8 and tumor necrosis factor in patients with Helicobacter pylori infection, J. Clin. Pathol. 48:133–136.

    Article  PubMed  CAS  Google Scholar 

  103. Noach, L.A., Bosma, N.B., Jansen, J., Hoek, F.J., vanDeventer, S.J.H., and Tytgat, G.N.J., 1994, Mucosal tumor necrosis factor-a, interleukin IB and interleukin-8 production in patients with Helicobacter pylori infection, Scand. J. Gastroenterol. 29:425–429.

    Article  PubMed  CAS  Google Scholar 

  104. Fox, J., Blanco, M., Murphy, J., Taylor, J.N., Lee, A., Kabok, Z., and Pappo, J., 1993, Local and systemic immune responses in murine Helicobacter felis active chronic gastritis, Infect. Immun. 61:2309–2315.

    PubMed  CAS  Google Scholar 

  105. Papadimitriou, C., Elli, I.-V., Tsianos E., and Moutsopoulos H., 1988, Epithelial HLA-DR expression and lymphocyte subsets in gastric mucosa in type B chronic gastritis, Vir. Arch. Pathol. Anat. 413:197–204.

    Article  CAS  Google Scholar 

  106. Engstrand, L., Scheynius, A., Pahison, L., Grimelius, L., Schwan, A., and Gustavsson, S., 1989, Association of Campylobacter pylori with induced expression of class II transplantation antigens on gastric epithelial cells, Infect. Immun. 57:827–832.

    PubMed  CAS  Google Scholar 

  107. Valnes, K., Huitfeldt, H.S., and Brandzaeg, P., 1990, Relation between T cell number and epithelial HLA class II expression quantified by image analysis in normal and inflamed human gastric mucosa, Gut 31:647–652.

    Article  PubMed  CAS  Google Scholar 

  108. Weiner, H.L., Friedman, A., Miller, A., Khoury, S.J., Al-sabbagh, A., Santos, L., Sayegh, M., Nussenblatt, R.B., Trentham, D.E., and Hafler, D.A., 1994, Oral tolerance: Immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens, Ann. Rev. Immunol. 12:809–837.

    Article  CAS  Google Scholar 

  109. Vega-Lopez, M., Telemo, E., Bailey, M., Stevens, K., and Stokes, C., 1993, Immune cell distribution in the small intestine of the pig: Immunohistochemical evidence for an organized compartmentalization in the lamina propria, Vet. Immunol. Immunopathol. 37:49–60.

    Article  PubMed  CAS  Google Scholar 

  110. Kaiserlain, D., and Vidal, K., 1993, Antigen presentation by intestinal epithelial cells, Immunol. Today 14:115.

    Article  Google Scholar 

  111. Dixon, M.F., Wyatt, J.L., Baarke, D.A., and Rathbone, B.J., 1988, Lymphocytic gastritis-relationship to Campylobacter pylori infection, J. Pathol. 154:125–132.

    Article  PubMed  CAS  Google Scholar 

  112. Wyatt, J.I., 1995, Histopathology of gastroduodenal inflammation: The impact of Helicobacter pylori, Histopathol. 26:1–15.

    Article  CAS  Google Scholar 

  113. Price, A.B., 1991, The Sydney system: Histological division, J. Gastroenterol. Hepatol. 6:209–222.

    Article  PubMed  CAS  Google Scholar 

  114. Campbell, P.A., 1990, The neutrophil, a professional killer of bacteria may be controloled by T cells, Clin. Exp. Immunol. 79:141–143.

    Article  PubMed  CAS  Google Scholar 

  115. Goodman, 1992, Molecular cloning of porcine alveolar macrophage-derived neutrophil chemotactic factors I and II: Identification of porcine IL-8 and another intercrine-alpha protein, Biochem. 31:10483–10490.

    Article  CAS  Google Scholar 

  116. Deem, R.L., Shanahan, F., Targan, S.R., 1991, Triggered human mucosal T cells release tumour necrosis factor alpha and interferon-gamma which kill human colonic epithelial cells, Clin. Exp. Immunol. 83:79–84.

    Article  PubMed  CAS  Google Scholar 

  117. Karttunen, R.G., Andersson, K., Poikonen, T.U., Kosunen, T., Kartunen, K., Juuniten, K., and Niemala, S., 1990, Helicobacter pylori induce lymphocyte activation in peripheral blood cultures, Clin. Exp. Immunol. 82:485–488.

    Article  PubMed  CAS  Google Scholar 

  118. Alper, J., 1993., Ulcers as an infectious disease, Science 260:159–160.

    Article  PubMed  CAS  Google Scholar 

  119. Morfitt, D.C., and Pohlenz, J.F.M., 1989, Porcine colonic lymphoglandular complex: Distribution, structure and epithelium, Am. J. Anat. 184:41–51.

    Article  PubMed  CAS  Google Scholar 

  120. Graham, D.Y., 1991, Helicobacter pylori: Its epidemiology and its role in duodenal ulcer disease, J. Gastroenterol. Hepatol. 6:105–113.

    Article  PubMed  CAS  Google Scholar 

  121. Lee, A., 1993, H pylori-initiated ulcerogenesis: Look to the host, Lancet 341:280–281.

    Article  PubMed  CAS  Google Scholar 

  122. Peterson, W.L., 1991, Helicobacter pylori and peptic ulcer disease, N. Eng. J. Med. 324:1043–1048.

    Article  CAS  Google Scholar 

  123. Blaser, M.J., and Parsonnet J., 1994, Parasitism by the “slow” bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia, J. Clin. Invest. 94:4–8.

    Article  PubMed  CAS  Google Scholar 

  124. Buck, G.E., 1990, Campylobacter pylori and gastroduodenal disease, Clin. Microbiol. Rev. 3:1–12.

    PubMed  CAS  Google Scholar 

  125. Graham, D.Y., Lew, G.M., Klein, P.D., Evans, D.G., Evans, J.D., Jr., Saeed, Z.A., and, Malaty, H.F., 1992, Effect of treatment of Helicobacter pylori infection on long-term recurrence of gastric or duodenal ulcer; a randomized controlled study, Ann. Int. Med. 116:705–708.

    PubMed  CAS  Google Scholar 

  126. Hassal, E., and Dimmick, J.E., 1991, Unique features of Helicobacter pylori disease in childern, Dig. Dis. Sci. 36:417–423.

    Article  Google Scholar 

  127. NIH consensus statement, 1994, Helicobacter pylori in peptic ulcer disease, Feb. 7.

    Google Scholar 

  128. Hentschel, E.G., Brandstatter, B., Dragosics, A.M., Hirschl, H., Nemec, K., Schutze, M., and Wurzer, H., 1993, Effect of ranitidine and amoxicillin plus metronidazole on the eradication of H. pylori and recurrence of duodenal ulcer, N. Eng. J. Med. 328:308–312.

    Article  CAS  Google Scholar 

  129. Marshall, B.J., Warren, J.B., and Blincow, E.D., 1988, Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori, Lancet ii: 1437–1442.

    Article  Google Scholar 

  130. Eaton, K.A., and Krakowka, S., 1995, Avirulent, urease-deficient Helicobacter pylori colonizes gastric epithelial explants ex vivo, Scand. J. Gastroenterol. 30:434–437.

    Article  PubMed  CAS  Google Scholar 

  131. Katz, J., 1991, The course of peptic ulcer disease, Med. Clin. N. Am. 75:831–840.

    PubMed  CAS  Google Scholar 

  132. Lee, A., 1994, The microbiology and epidemiology of Helicobacter pylori infection, Scand. J. Gastroenterol. 29(Suppl 201):2–6.

    Article  Google Scholar 

  133. O’Connor, H.J., 1994, The role of Helicobacter pylori in peptic ulcer disease, Scand. J Gastroenterol. 29(Suppl 201):11–15.

    Article  Google Scholar 

  134. Taylor, D., and Blaser, M., 1991, The epidemiology of Helicobacter pylori infection, Epidemiol. Rev. 13:42–59.

    PubMed  CAS  Google Scholar 

  135. Lee, A., Fox, J., and Hazell, S., 1993, Pathogenicity of Helicobacter pylori: Aperspective, Infect. Immun. 61:1601–1610.

    PubMed  CAS  Google Scholar 

  136. Leung, K., Hui, M., Chan, P.K., and Thomas, T.M.M., 1992, Helicobacter pylori-related gastritis and gastric ulcer. A continumum of progressive epithelial degeneration, Am. J. Clin. Pathol. 6:569–574.

    Google Scholar 

  137. Clearfield, H.R., 1991, Helicobacter pylori: Aggressor or innocent bystander? Med. Clin. N. Am. 75:815–829.

    PubMed  CAS  Google Scholar 

  138. Louw, J.A., van Rensburg, C., Zak, J., Adams. G., and Marks, I.N., 1993, Distribution of Helicobacter pylori colonization and associated gastric inflammatory changes: Difference between patients with duodenal and gastric ulcers, J. Clin. Pathol. 46:754–756.

    Article  PubMed  CAS  Google Scholar 

  139. Moss, S., and Calam, J., 1992, Helicobacter pylori and peptic ulcers: The present position, Gut 33:289–292.

    Article  PubMed  CAS  Google Scholar 

  140. Sipponen, P., and Hyvarinen, H., 1993, Role of Helicobacter pylori in the pathogenesis of gastritis, peptic ulcer and gastric cancer, Scand. J. Gastroenterol. 28(Suppl 196):3–6.

    Article  Google Scholar 

  141. Bui, H.X., del Rosario, A., Sonbati, H., Lee, C.Y., George, M., and Ross, J.S., 1991, Helicobacter pylori affects the quality of experimental gastric ulcer healing in a new animal model, Exp. Mol. Pathol. 55:261–268.

    Article  PubMed  CAS  Google Scholar 

  142. Genta, R., Hamner, H.W., and Graham, D.Y., 1993, Gastric lymphoid follicles in Helicobacter pylori infection: Frequency, distribution, and response to triple therapy, Human Pathol. 24:577–583.

    Article  CAS  Google Scholar 

  143. Mai, U., Perez-Perez, G., Allen, J., Wahl, S., Blazer, M., and Smith P., 1992, Surface proteins from Helicobacter pylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa, J. Exptl.Med. 175:517–525.

    Article  CAS  Google Scholar 

  144. Chang, K.Y., Wyle, F., Stachura, J., and Tarnawski, A., 1993, Helicobacter pylori toxin delays healing of experimental gastric ulcers and inhibits cell proliferation at the ulcer margin, Gastroenterol. 104:52 (Abstr.).

    Google Scholar 

  145. Rautelin, H., Blomberg, B., Fredlund, H., Jarnerot, G., and Danielsson, D., 1993, Incidence of Helicobacter pylori activating neutrophils in patients with peptic ulcer disease, Gut 34:599–603.

    Article  PubMed  CAS  Google Scholar 

  146. Reymunde, A., Deren, M.D., Nachamkin, I., Oppenheim, D., and Weinbaum, G., 1993, Production of chemoattractant by Helicobacter pylori, Digest. Dis. Sci 38:1697–1701.

    Article  PubMed  CAS  Google Scholar 

  147. Cover, T.L., Cao, P., Murthy, U.K., Sipple, M.S., and Blaser, M.J., 1992, Serum neutralizing antibody response to the vacuolation cytotoxin of Helicobacter pylori, Clin. Invest. 90:913–918.

    Article  CAS  Google Scholar 

  148. Nielsen, H., and Andersen, L., 1992, Chemotactic activity of Helicobacter pylori sonicate for human polymorphonuclear leucocytes and monocytes, Gut 33:738–742.

    Article  PubMed  CAS  Google Scholar 

  149. Brandtzaeg, P., Bjerke, K., Kett, K., Kvale, D., Rognum, D.O., Scott, H., Sollid, I.M., and Valnes, K., 1987, Production and secretion of immunoglobulin in the gastrointestinal tract, Trans. Ann. Allerg. 59:21–39.

    CAS  Google Scholar 

  150. Megraud, F., Neman-Simha, V., and Brugmann, D., 1992, Further evidence of the toxic effect of ammonia produced by Helicobacter pylori urease on human epithelial cells, Infect. Immun. 60:1858–1863.

    PubMed  CAS  Google Scholar 

  151. Sidebotham, R.L., Batten, J.J., Karim, Q.N., Spencer, J., and Baron, J.H., 1991, Breakdown of gastric mucus in presence of Helicobacter pylori, J. Clin. Pathol. 44:52–57.

    Article  PubMed  CAS  Google Scholar 

  152. Sidebotham, R.L., and Baron, J.H., 1990, Hypothesis; Helicobacter pylori, urease, mucus, and gastric ulcer, Lancet 355:193–195.

    Article  Google Scholar 

  153. Correa, P., 1992, Human gastric carninogenesis: A multistep and multifactorial process — First American Cancer Society Award Lecture on Cancer epidemiology and Prevention, Cancer Res. 52:6735–6740.

    PubMed  CAS  Google Scholar 

  154. Correa, P., Fox, J., Fontham, E., Ruiz, B., Lin, Y., Taylor, N., Mackinley, D., de Lima, E., Portilla, H. and Zarama, G., 1990, Helicobacter pylori and gastric carcinoma, Cancer 66:2569–2674.

    Article  PubMed  CAS  Google Scholar 

  155. Correa, P., and Shiao, Y.-H., 1994, Phenotypic and genotypic events in gastric carcino-genesis, Cancer Res. 54:1941s–1943s.

    PubMed  CAS  Google Scholar 

  156. Fox, J.G., Correa, P., Taylor, N.S., Zavala, D., Fontham, E., Janney, P.H., Rodrigeuz, E., Hunter, F., and Diavolitis, S., 1989, Campylobacter pylori-associated gastritis and immune response in a population at increased risk of gastric carcinoma, Am. J. Gastroenterol. 32:775–781.

    Google Scholar 

  157. Forman, D., 1991, Helicobacter pylori infection: A novel risk factor in the etiology of gastric cancer, J. Natl. Cancer Inst. 83:1702–1703.

    Article  PubMed  CAS  Google Scholar 

  158. Parsonnet, J., Vandersteen, J.D., Goates, J., Sibley, R.K., Sibley, J., and Chang, Y., 1991, Helicobacter pylori infection in intestinal-and diffuse-type gastric adenocarcinomas, J. Natl. Cancer Inst. 93:640–643.

    Article  Google Scholar 

  159. Engstrand L., 1995, Potential animal models of Helicobacter pylori infection in immunological and vaccine research, FEMS Immunol. Med. Microbiol. 10:265–270.

    Article  PubMed  CAS  Google Scholar 

  160. Michetti, P., Corthesy-Theulaz, I., Davin, C., Haas, R., Vaney, A-C., Heitz, M., Bille, J., Kraehenbuhl, J-R, Saraga, E., and Blum, A.L., 1994, Immunization of BALB/c mice against Helicobacter felis infection with Helicobacter pylori urease, Gasterenterol. 107:1002–1011.

    CAS  Google Scholar 

  161. Pappo, J., Thomas, W.D., Kabok, Z., Taylor, N.S., Murphy, J., and Fox, J.G., 1995, Effect of oral immunization with recombinant urease on murine Helicobacter felis gastritis, Infect. Immun. 63:1246–1252.

    PubMed  CAS  Google Scholar 

  162. Czinn, S., and Nedrud, J.G., 1991, Oral immunization against Helicobacter pylori, Infect. Immun. 59:2359–2364.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Veterinary Biosciences College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, Columbus, OH, 43210, USA

    Dr. Steven Krakowka & Kathryn A. Eaton

Authors
  1. Dr. Steven Krakowka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathryn A. Eaton
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Illinois, Urbana, Illinois, USA

    Mike E. Tumbleson

  2. University of Minnesota, St. Paul, Minnesota, USA

    Lawrence B. Schook

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer Science+Business Media New York

About this chapter

Cite this chapter

Krakowka, S., Eaton, K.A. (1996). Helicobacter pylori Infection in Gnotobiotic Piglets. In: Tumbleson, M.E., Schook, L.B. (eds) Advances in Swine in Biomedical Research. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5885-9_32

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5885-9_32

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7699-6

  • Online ISBN: 978-1-4615-5885-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation