Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1992 Sep;141(3):721–727.

Helicobacter pylori. Its role in the pathogenesis of peptic ulcer disease in a new animal model.

J S Ross 1, H X Bui 1, A del Rosario 1, H Sonbati 1, M George 1, C Y Lee 1
PMCID: PMC1886702  PMID: 1519673

Abstract

The association and causative role of Helicobacter pylori infection of the stomach with gastric ulcer, duodenal ulcer, non-ulcer dyspepsia, and gastritis has remained controversial. The authors studied the effects of daily intragastric administration of H. pylori suspension in saline (10(8) CFU/ml) and bacteria-free filtrates of saline H. pylori suspensions in 85 Sprague-Dawley rats (weight, 150 to 200 g) with normal mucosa and with surgically produced experimental gastric ulcers. Group I rats (n = 30) with pre-existent experimental gastric ulcers received H. pylori suspension (ATCC 43504, 10(8) CFU/ml); Group II rats (n = 20) with experimental gastric ulcers received bacteria-free H. pylori filtrates; Group III rats with ulcers (n = 20) received saline alone; and Group IV control rats (n = 15) without ulcers received intact H. pylori organisms in suspension (ATCC 43504, 10(8) CFU/ml). At death, ulcer surface areas were measured with a dissecting microscope. Full-thickness sections were obtained for quantitative and qualitative histologic parameters, including the area of remaining mucosal necrosis; characteristics and cellular composition of restored mucosal architectures; and presence or absence of inflammation including counts of neutrophils and lymphocytes. H. pylori organisms were identified within the surface mucus and crypts using routine, special, and immunohistochemical stains. Our results indicate that the continued presence of either intact H. pylori organisms or bacteria-free H. pylori filtrates in the stomachs of rats with pre-existent gastric ulcers resulted in delayed healing of the ulcers and persistence of chronic active inflammation. Daily administration of suspensions of H. pylori organisms to sham-operated rats with intact gastric mucosa, however, resulted in no ulceration or inflammation despite identification of surface H. pylori organisms at death. The authors conclude that H. pylori alone causes little or no effect on an intact gastric mucosa in the rat, that either intact organisms or bacteria-free filtrates cause similar prolongation and delayed healing of pre-existing ulcers with active chronic inflammation, and that the presence of predisposing factors leading to disruption of gastric mucosal integrity may be required for the H. pylori enhancement of inflammation and tissue damage in the stomach.

Full text

PDF
721

Images in this article

723Figure 1
on p.723
723Figure 2
on p.723
724Figure 3
on p.724
724Figure 4
on p.724
724Figure 5
on p.724

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baskerville A., Newell D. G. Naturally occurring chronic gastritis and C pylori infection in the rhesus monkey: a potential model for gastritis in man. Gut. 1988 Apr;29(4):465–472. doi: 10.1136/gut.29.4.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blaser M. J. Gastric Campylobacter-like organisms, gastritis, and peptic ulcer disease. Gastroenterology. 1987 Aug;93(2):371–383. doi: 10.1016/0016-5085(87)91028-6. [DOI] [PubMed] [Google Scholar]
  3. Bronsdon M. A., Schoenknecht F. D. Campylobacter pylori isolated from the stomach of the monkey, Macaca nemestrina. J Clin Microbiol. 1988 Sep;26(9):1725–1728. doi: 10.1128/jcm.26.9.1725-1728.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bui H. X., del Rosario A., Sonbati H., Lee C. Y., George M., Ross J. S. Helicobacter pylori affects the quality of experimental gastric ulcer healing in a new animal model. Exp Mol Pathol. 1991 Dec;55(3):261–268. doi: 10.1016/0014-4800(91)90006-j. [DOI] [PubMed] [Google Scholar]
  5. Campylobacter-like organisms in the stomach of patients and healthy individuals. Lancet. 1984 Jun 16;1(8390):1348–1349. [PubMed] [Google Scholar]
  6. Chen X. G., Correa P., Offerhaus J., Rodriguez E., Janney F., Hoffmann E., Fox J., Hunter F., Diavolitsis S. Ultrastructure of the gastric mucosa harboring Campylobacter-like organisms. Am J Clin Pathol. 1986 Nov;86(5):575–582. doi: 10.1093/ajcp/86.5.575. [DOI] [PubMed] [Google Scholar]
  7. Coghlan J. G., Gilligan D., Humphries H., McKenna D., Dooley C., Sweeney E., Keane C., O'Morain C. Campylobacter pylori and recurrence of duodenal ulcers--a 12-month follow-up study. Lancet. 1987 Nov 14;2(8568):1109–1111. doi: 10.1016/s0140-6736(87)91545-5. [DOI] [PubMed] [Google Scholar]
  8. Dooley C. P., Cohen H. The clinical significance of Campylobacter pylori. Ann Intern Med. 1988 Jan;108(1):70–79. doi: 10.7326/0003-4819-108-1-70. [DOI] [PubMed] [Google Scholar]
  9. Dubois A., Tarnawski A., Newell D. G., Fiala N., Dabros W., Stachura J., Krivan H., Heman-Ackah L. M. Gastric injury and invasion of parietal cells by spiral bacteria in rhesus monkeys. Are gastritis and hyperchlorhydria infectious diseases? Gastroenterology. 1991 Apr;100(4):884–891. doi: 10.1016/0016-5085(91)90260-r. [DOI] [PubMed] [Google Scholar]
  10. Fox J. G., Correa P., Taylor N. S., Lee A., Otto G., Murphy J. C., Rose R. Helicobacter mustelae-associated gastritis in ferrets. An animal model of Helicobacter pylori gastritis in humans. Gastroenterology. 1990 Aug;99(2):352–361. doi: 10.1016/0016-5085(90)91016-y. [DOI] [PubMed] [Google Scholar]
  11. Goodwin C. S., Armstrong J. A., Marshall B. J. Campylobacter pyloridis, gastritis, and peptic ulceration. J Clin Pathol. 1986 Apr;39(4):353–365. doi: 10.1136/jcp.39.4.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Graham D. Y. Campylobacter pylori and peptic ulcer disease. Gastroenterology. 1989 Feb;96(2 Pt 2 Suppl):615–625. doi: 10.1016/s0016-5085(89)80057-5. [DOI] [PubMed] [Google Scholar]
  13. Hazell S. L., Hennessy W. B., Borody T. J., Carrick J., Ralston M., Brady L., Lee A. Campylobacter pyloridis gastritis II: Distribution of bacteria and associated inflammation in the gastroduodenal environment. Am J Gastroenterol. 1987 Apr;82(4):297–301. [PubMed] [Google Scholar]
  14. Hazell S. L., Lee A., Brady L., Hennessy W. Campylobacter pyloridis and gastritis: association with intercellular spaces and adaptation to an environment of mucus as important factors in colonization of the gastric epithelium. J Infect Dis. 1986 Apr;153(4):658–663. doi: 10.1093/infdis/153.4.658. [DOI] [PubMed] [Google Scholar]
  15. Hupertz V., Czinn S. Demonstration of a cytotoxin from Campylobacter pylori. Eur J Clin Microbiol Infect Dis. 1988 Aug;7(4):576–578. doi: 10.1007/BF01962619. [DOI] [PubMed] [Google Scholar]
  16. Jones D. M., Lessells A. M., Eldridge J. Campylobacter like organisms on the gastric mucosa: culture, histological, and serological studies. J Clin Pathol. 1984 Sep;37(9):1002–1006. doi: 10.1136/jcp.37.9.1002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kirk R. M. Are gastric and duodenal ulcers separate diseases or do they form a continuum? Dig Dis Sci. 1981 Feb;26(2):149–154. doi: 10.1007/BF01312235. [DOI] [PubMed] [Google Scholar]
  18. Leunk R. D., Johnson P. T., David B. C., Kraft W. G., Morgan D. R. Cytotoxic activity in broth-culture filtrates of Campylobacter pylori. J Med Microbiol. 1988 Jun;26(2):93–99. doi: 10.1099/00222615-26-2-93. [DOI] [PubMed] [Google Scholar]
  19. Loffeld R. J., Potters H. V., Arends J. W., Stobberingh E., Flendrig J. A., van Spreeuwel J. P. Campylobacter associated gastritis in patients with non-ulcer dyspepsia. J Clin Pathol. 1988 Jan;41(1):85–88. doi: 10.1136/jcp.41.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Logan R. P., Gummett P. A., Misiewicz J. J., Karim Q. N., Walker M. M., Baron J. H. One week eradication regimen for Helicobacter pylori. Lancet. 1991 Nov 16;338(8777):1249–1252. doi: 10.1016/0140-6736(91)92111-e. [DOI] [PubMed] [Google Scholar]
  21. Luck J. M., Seth T. N. Gastric Urease. Biochem J. 1924;18(6):1227–1231. doi: 10.1042/bj0181227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mai U. E., Perez-Perez G. I., Wahl L. M., Wahl S. M., Blaser M. J., Smith P. D. Soluble surface proteins from Helicobacter pylori activate monocytes/macrophages by lipopolysaccharide-independent mechanism. J Clin Invest. 1991 Mar;87(3):894–900. doi: 10.1172/JCI115095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Marshall B. J., Armstrong J. A., McGechie D. B., Glancy R. J. Attempt to fulfil Koch's postulates for pyloric Campylobacter. Med J Aust. 1985 Apr 15;142(8):436–439. doi: 10.5694/j.1326-5377.1985.tb113443.x. [DOI] [PubMed] [Google Scholar]
  24. Marshall B. J., Goodwin C. S., Warren J. R., Murray R., Blincow E. D., Blackbourn S. J., Phillips M., Waters T. E., Sanderson C. R. Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet. 1988 Dec 24;2(8626-8627):1437–1442. doi: 10.1016/s0140-6736(88)90929-4. [DOI] [PubMed] [Google Scholar]
  25. Marshall B. J., McGechie D. B., Rogers P. A., Glancy R. J. Pyloric Campylobacter infection and gastroduodenal disease. Med J Aust. 1985 Apr 15;142(8):439–444. doi: 10.5694/j.1326-5377.1985.tb113444.x. [DOI] [PubMed] [Google Scholar]
  26. McNulty C. A., Watson D. M. Spiral bacteria of the gastric antrum. Lancet. 1984 May 12;1(8385):1068–1069. doi: 10.1016/s0140-6736(84)91469-7. [DOI] [PubMed] [Google Scholar]
  27. Morris A., Nicholson G. Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol. 1987 Mar;82(3):192–199. [PubMed] [Google Scholar]
  28. Ormand J. A., Talley N. J. Campylobacter pylori, mucus, and peptic ulceration. A dynamic interaction. J Clin Gastroenterol. 1989 Oct;11(5):492–495. doi: 10.1097/00004836-198910000-00002. [DOI] [PubMed] [Google Scholar]
  29. Price A. B., Levi J., Dolby J. M., Dunscombe P. L., Smith A., Clark J., Stephenson M. L. Campylobacter pyloridis in peptic ulcer disease: microbiology, pathology, and scanning electron microscopy. Gut. 1985 Nov;26(11):1183–1188. doi: 10.1136/gut.26.11.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rollason T. P., Stone J., Rhodes J. M. Spiral organisms in endoscopic biopsies of the human stomach. J Clin Pathol. 1984 Jan;37(1):23–26. doi: 10.1136/jcp.37.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Steer H. W. Surface morphology of the gastroduodenal mucosa in duodenal ulceration. Gut. 1984 Nov;25(11):1203–1210. doi: 10.1136/gut.25.11.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Steer H. W. The gastro-duodenal epithelium in peptic ulceration. J Pathol. 1985 Aug;146(4):355–362. doi: 10.1002/path.1711460409. [DOI] [PubMed] [Google Scholar]
  33. Tatsuta M., Iishi H., Okuda S. Location of peptic ulcers in relation to antral and fundal gastritis by chromoendoscopic follow-up examinations. Dig Dis Sci. 1986 Jan;31(1):7–11. doi: 10.1007/BF01347902. [DOI] [PubMed] [Google Scholar]
  34. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983 Jun 4;1(8336):1273–1275. [PubMed] [Google Scholar]
  35. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983 Jun 4;1(8336):1273–1275. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES