Skip to main content
NCBI home page
Gut logoLink to Gut
. 1992 Jul;33(7):902–908. doi: 10.1136/gut.33.7.902

Surface epithelium related activation of complement differs in Crohn's disease and ulcerative colitis.

T S Halstensen 1, T E Mollnes 1, P Garred 1, O Fausa 1, P Brandtzaeg 1
PMCID: PMC1379402  PMID: 1379568

Abstract

IgG1 and activated complement are colocalised on the colonic epithelial brush border in active ulcerative colitis. To investigate whether such deposition is specific for ulcerative colitis, we examined ethanol fixed mucosal specimens from 18 patients with Crohn's colitis and 14 with terminal ileitis by indirect two colour immunofluorescence staining. Monoclonal antibodies to the IgG subclasses and to neoepitopes of activated complement C3b and the terminal complement complex were used in combination with rabbit antiserum to C1q, C4c or cytokeratin. Granular deposition of C3b and terminal complement complex were observed at the luminal face of the surface epithelium in 10 of 18 patients with Crohn's colitis. Specimens from eight of 14 patients with ileal involvement were intensely stained for activated complement (primarily C3b) within the surface mucus layer. No epithelial IgG, C1q or C4c deposition was observed. The results suggest that early and late phase complement activation takes place at the luminal face of the epithelium in Crohn's disease. The absence of colocalised IgG and complement components involved in the classical activation pathway (C1q and C4c), however, suggest that other immunopathological mechanisms (the alternative pathway?) are primarily involved in Crohn's disease in contrast with ulcerative colitis.

Full text

PDF
902

Images in this article

903Figure 1
on p.903
905Figure 3
on p.905
905Figure 4
on p.905
905Figure 5
on p.905
906Figure 6
on p.906

Selected References

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

  1. Ahrenstedt O., Knutson L., Nilsson B., Nilsson-Ekdahl K., Odlind B., Hällgren R. Enhanced local production of complement components in the small intestines of patients with Crohn's disease. N Engl J Med. 1990 May 10;322(19):1345–1349. doi: 10.1056/NEJM199005103221903. [DOI] [PubMed] [Google Scholar]
  2. Aluwihare A. P. Electron microscopy in Crohn's disease. Gut. 1971 Jul;12(7):509–518. doi: 10.1136/gut.12.7.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Auer I. O., Röder A., Wensinck F., van de Merwe J. P., Schmidt H. Selected bacterial antibodies in Crohn's disease and ulcerative colitis. Scand J Gastroenterol. 1983 Mar;18(2):217–223. doi: 10.3109/00365528309181586. [DOI] [PubMed] [Google Scholar]
  4. Bagchi S., Das K. M. Detection and partial characterization of Crohn's disease tissue specific proteins recognized by Crohn's disease sera. Clin Exp Immunol. 1984 Jan;55(1):41–48. [PMC free article] [PubMed] [Google Scholar]
  5. Baklien K., Brandtzaeg P. Comparative mapping of the local distribution of immunoglobulin-containing cells in ulcerative colitis and Crohn's disease of the colon. Clin Exp Immunol. 1975 Nov;22(2):197–209. [PMC free article] [PubMed] [Google Scholar]
  6. Brandtzaeg P. Mucosal and glandular distribution of immunoglobulin components. Immunohistochemistry with a cold ethanol-fixation technique. Immunology. 1974 Jun;26(6):1101–1114. [PMC free article] [PubMed] [Google Scholar]
  7. Brandtzaeg P., Rognum T. O. Evaluation of tissue preparation methods and paired immunofluorescence staining for immunocytochemistry of lymphomas. Histochem J. 1983 Jul;15(7):655–689. doi: 10.1007/BF01002987. [DOI] [PubMed] [Google Scholar]
  8. Butcher P. D., McFadden J. J., Hermon-Taylor J. Investigation of mycobacteria in Crohn's disease tissue by Southern blotting and DNA hybridisation with cloned mycobacterial genomic DNA probes from a Crohn's disease isolated mycobacteria. Gut. 1988 Sep;29(9):1222–1228. doi: 10.1136/gut.29.9.1222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chiodini R. J., Van Kruiningen H. J., Thayer W. R., Coutu J. A. Spheroplastic phase of mycobacteria isolated from patients with Crohn's disease. J Clin Microbiol. 1986 Sep;24(3):357–363. doi: 10.1128/jcm.24.3.357-363.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chiodini R. J., Van Kruiningen H. J., Thayer W. R., Merkal R. S., Coutu J. A. Possible role of mycobacteria in inflammatory bowel disease. I. An unclassified Mycobacterium species isolated from patients with Crohn's disease. Dig Dis Sci. 1984 Dec;29(12):1073–1079. doi: 10.1007/BF01317078. [DOI] [PubMed] [Google Scholar]
  11. Claus D. R., Siegel J., Petras K., Osmand A. P., Gewurz H. Interactions of C-reactive protein with the first component of human complement. J Immunol. 1977 Jul;119(1):187–192. [PubMed] [Google Scholar]
  12. Dahlbäck K., Löfberg H., Dahlbäck B. Localization of vitronectin (S-protein of complement) in normal human skin. Acta Derm Venereol. 1986;66(6):461–467. [PubMed] [Google Scholar]
  13. Elmgreen J., Berkowicz A., Sørensen H. Hypercatabolism of complement in Crohn's disease--assessment of circulating C3c. Acta Med Scand. 1983;214(5):403–407. doi: 10.1111/j.0954-6820.1983.tb08615.x. [DOI] [PubMed] [Google Scholar]
  14. Fujiwara M., Watanabe H. Responsiveness of T cells to mutant major histocompatibility complex class I antigen. I. Obligatory dependence of proliferative response on the presence of stimulator type accessory cells. Scand J Immunol. 1988 Mar;27(3):311–318. doi: 10.1111/j.1365-3083.1988.tb02352.x. [DOI] [PubMed] [Google Scholar]
  15. Graham D. Y., Markesich D. C., Yoshimura H. H. Mycobacteria and inflammatory bowel disease. Results of culture. Gastroenterology. 1987 Feb;92(2):436–442. doi: 10.1016/0016-5085(87)90139-9. [DOI] [PubMed] [Google Scholar]
  16. Halstensen T. S., Mollnes T. E., Brandtzaeg P. Persistent complement activation in submucosal blood vessels of active inflammatory bowel disease: immunohistochemical evidence. Gastroenterology. 1989 Jul;97(1):10–19. doi: 10.1016/0016-5085(89)91409-1. [DOI] [PubMed] [Google Scholar]
  17. Halstensen T. S., Mollnes T. E., Fausa O., Brandtzaeg P. Deposits of terminal complement complex (TCC) in muscularis mucosae and submucosal vessels in ulcerative colitis and Crohn's disease of the colon. Gut. 1989 Mar;30(3):361–366. doi: 10.1136/gut.30.3.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Halstensen T. S., Mollnes T. E., Garred P., Fausa O., Brandtzaeg P. Epithelial deposition of immunoglobulin G1 and activated complement (C3b and terminal complement complex) in ulcerative colitis. Gastroenterology. 1990 May;98(5 Pt 1):1264–1271. doi: 10.1016/0016-5085(90)90343-y. [DOI] [PubMed] [Google Scholar]
  19. Hodgson H. J., Potter B. J., Jewell D. P. C3 metabolism in ulcerative colitis and Crohn's disease. Clin Exp Immunol. 1977 Jun;28(3):490–495. [PMC free article] [PubMed] [Google Scholar]
  20. Hodgson H. J., Potter B. J., Jewell D. P. Humoral immune system in inflammatory bowel disease: I. Complement levels. Gut. 1977 Sep;18(9):749–753. doi: 10.1136/gut.18.9.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hostetter M. K., Lorenz J. S., Preus L., Kendrick K. E. The iC3b receptor on Candida albicans: subcellular localization and modulation of receptor expression by glucose. J Infect Dis. 1990 Apr;161(4):761–768. doi: 10.1093/infdis/161.4.761. [DOI] [PubMed] [Google Scholar]
  22. Huitfeldt H. S., Brandtzaeg P. Various keratin antibodies produce immunohistochemical staining of human myocardium and myometrium. Histochemistry. 1985;83(5):381–389. doi: 10.1007/BF00509196. [DOI] [PubMed] [Google Scholar]
  23. Jefferis R., Reimer C. B., Skvaril F., de Lange G., Ling N. R., Lowe J., Walker M. R., Phillips D. J., Aloisio C. H., Wells T. W. Evaluation of monoclonal antibodies having specificity for human IgG sub-classes: results of an IUIS/WHO collaborative study. Immunol Lett. 1985;10(3-4):223–252. doi: 10.1016/0165-2478(85)90082-3. [DOI] [PubMed] [Google Scholar]
  24. Kett K., Rognum T. O., Brandtzaeg P. Mucosal subclass distribution of immunoglobulin G-producing cells is different in ulcerative colitis and Crohn's disease of the colon. Gastroenterology. 1987 Nov;93(5):919–924. doi: 10.1016/0016-5085(87)90552-x. [DOI] [PubMed] [Google Scholar]
  25. Kobayashi K., Blaser M. J., Brown W. R. Immunohistochemical examination for mycobacteria in intestinal tissues from patients with Crohn's disease. Gastroenterology. 1989 Apr;96(4):1009–1015. doi: 10.1016/0016-5085(89)91617-x. [DOI] [PubMed] [Google Scholar]
  26. Kovacsovics T., Tschopp J., Kress A., Isliker H. Antibody-independent activation of C1, the first component of complement, by cardiolipin. J Immunol. 1985 Oct;135(4):2695–2700. [PubMed] [Google Scholar]
  27. Lake A. M., Stitzel A. E., Urmson J. R., Walker W. A., Spitzer R. E. Complement alterations in inflammatory bowel disease. Gastroenterology. 1979 Jun;76(6):1374–1379. [PubMed] [Google Scholar]
  28. Markesich D. C., Graham D. Y., Yoshimura H. H. Progress in culture and subculture of spheroplasts and fastidious acid-fast bacilli isolated from intestinal tissues. J Clin Microbiol. 1988 Aug;26(8):1600–1603. doi: 10.1128/jcm.26.8.1600-1603.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mollnes T. E., Lea T., Harboe M., Tschopp J. Monoclonal antibodies recognizing a neoantigen of poly(C9) detect the human terminal complement complex in tissue and plasma. Scand J Immunol. 1985 Aug;22(2):183–195. doi: 10.1111/j.1365-3083.1985.tb01870.x. [DOI] [PubMed] [Google Scholar]
  30. Ratnoff W. D., Fearon D. T., Austen K. F. The role of antibody in the activation of the alternative complement pathway. Springer Semin Immunopathol. 1983;6(4):361–371. doi: 10.1007/BF02116280. [DOI] [PubMed] [Google Scholar]
  31. Scott M. G., Nahm M. H., Macke K., Nash G. S., Bertovich M. J., MacDermott R. P. Spontaneous secretion of IgG subclasses by intestinal mononuclear cells: differences between ulcerative colitis, Crohn's disease, and controls. Clin Exp Immunol. 1986 Oct;66(1):209–215. [PMC free article] [PubMed] [Google Scholar]
  32. Teisberg P., Gjone E. Humoral immune system activity in inflammatory bowel disease. Scand J Gastroenterol. 1975;10(5):545–549. [PubMed] [Google Scholar]
  33. Thyberg J., Graf W., Klingenström P. Intestinal fine structure in Crohn's disease. Lysosomal inclusions in epithelial cells and macrophages. Virchows Arch A Pathol Anat Histol. 1981;391(2):141–152. doi: 10.1007/BF00437592. [DOI] [PubMed] [Google Scholar]
  34. Veloso T. Complement deposits in inflammatory bowel disease. Gastroenterology. 1990 Nov;99(5):1541–1542. doi: 10.1016/0016-5085(90)91209-o. [DOI] [PubMed] [Google Scholar]
  35. Volanakis J. E., Kaplan M. H. Interaction of C-reactive protein complexes with the complement system. II. Consumption of guinea pig complement by CRP complexes: requirement for human C1q. J Immunol. 1974 Jul;113(1):9–17. [PubMed] [Google Scholar]
  36. Wakefield A. J., Sawyerr A. M., Dhillon A. P., Pittilo R. M., Rowles P. M., Lewis A. A., Pounder R. E. Pathogenesis of Crohn's disease: multifocal gastrointestinal infarction. Lancet. 1989 Nov 4;2(8671):1057–1062. doi: 10.1016/s0140-6736(89)91078-7. [DOI] [PubMed] [Google Scholar]
  37. van de Merwe J. P. The human faecal flora and Crohn's disease. Antonie Van Leeuwenhoek. 1984;50(5-6):691–700. doi: 10.1007/BF02386234. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES