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Changes in substance P-immunoreactive innervation of human colon associated with ulcerative colitis

  • Intestinal Disorders, Inflammatory Bowel Disease, Irritable Bowel Syndrome, and Immunology
  • Published:
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Abstract

The amount of colonic substance P and substance P-receptors is increased in ulcerative colitis, which may denote that substance-P is involved as a neurogenic mediator in the inflammatory process of ulcerative colitis. We studied the anatomical distribution of elevated colonic substance P in ulcerative colitis and assessed morphometrically wheter the changes in substance P correlate with alterations in colonic innervation. Full-thickness specimens of colonic wall were obtained from normal human colons (N=9) and the most and least affected regions of ulcerative colitis colons (N=10) and immunostained for substance P. Substance P immunoreactivity index was calculated by multiplying each intensity value by the number of pixels exhibiting this intensity value. The numbers of substance P-immunoreactive nerve fibers in the lamina propria were markedly increased, and their fluorescence intensity was enhanced in ulcerative colitis. The longitudinal muscle layer contained substance P-immunoreactive nerve fibers in ulcerative colitis, but not in the controls. The substance P-immunoreactive index (=number×intensity of nerve fibers) was 3.42±1.49 in controls, 21.19±7.79 in mild ulcerative colitis regions (P<0.05), and 29.68±9.81 in severe ulcerative colitis regions (P<0.01). Increase in the number of substance P nerve fibers is in accordance with the hypothesis that substance P contributes to neurogenic mediation of inflammation in ulcerative colitis.

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References

  1. Edwards FC, Truelove S: The course and prognosis of ulcerative colitis. I. Gut 4:299–315, 1963

    Google Scholar 

  2. Edwards FC, Truelove S: The course and prognosis of ulcerative colitis. III. Complications. Gut 5:1–22, 1964

    Google Scholar 

  3. Elson CO, Kagnoff MF, Fiocchi C, Befus AD, Targan S: Intestinal immunity and inflammation: Recent progress Gastroenterology 91:746–768, 1986

    Google Scholar 

  4. Mantyh PW, Catton M, Maggio JE, Vigna SR: Alterations in receptors for sensory neuropeptides in human inflammatory bowel disease. Adv Exp Med Biol 298:253–283, 1991.

    Google Scholar 

  5. Shanahan F, Anton P: Neuroendocrine modulation of the immune system. Possible implications for inflammatory bowel disease. Dig Dis Sci 33:41S-49S, 1988

    Google Scholar 

  6. Koch TR, Carney JA, Go VL: Distribution and quantitation of gut neuropeptides in normal intestine and inflammatory bowel diseases. Dig Dis Sci 32:369–376, 1987

    Google Scholar 

  7. Goldin E, Karmeli F, Selinger Z, Rachmilewitz D: Colonic substance P levels are increased in ulcerative colitis and decreased in chronic severe constipation. Dig Dis Sci 34:754–757, 1989

    Google Scholar 

  8. Mantyh CR, Gates TS, Zimmerman RP, Welton ML, Passaro EP Jr, Vigna SR, Maggio JE, Kruger L, Mantyh PW: Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn's disease. Proc Natl Acad Sci USA 85:3235–3239, 1988

    Google Scholar 

  9. Ferri GL, Botti PL, Vezzadi P, Biliotti G, Bloom SR, Polak JM: Peptide-containing innervation of the human intestinal mucosa. An immunohistochemical study on whole-mount preparations. Histochemistry 76:413–420, 1982

    Google Scholar 

  10. Ferri GL, Adrian TE, Ghatei MA, O'Shaughnessy DJ, Probert L, Lee YC, Buchan AM, Polak JM, Bloom SR: Tissue localization and relative distribution of regulatory peptides in separated layers from the human bowel. Gastroenterology 84:777–786, 1983.

    Google Scholar 

  11. Llewellyn Smith IJ, Furness JB, Murphy R, O'Brien PE, Costa M: Substance P-containing nerves in the human small intestine. Distribution, ultrastructure, and characterization of the immunoreactive peptide. Gastroenterology 86:421–435, 1984

    Google Scholar 

  12. Thayer WR, Spiro HM: Ileitis after ileostomy: Prestomal ileitis. Gastroenterology 42:547, 1962

    Google Scholar 

  13. Wattchow DA, Furness JB, Costa M: Distribution and coexistence of peptides in nerve fibers of the external muscle of the human gastrointestinal tract. Gastroenterology 95:32–41, 1988

    Google Scholar 

  14. Hoyle CH, Burnstock G: Neuronal populations in the submucous plexus of the human colon. J Anat 166:7–22, 1989

    Google Scholar 

  15. Crowe R, Kamm MA, Burnstock G, Lennard Jones JE: Peptide-containing neurons in different regions of the submucous plexus of human sigmoid colon. Gastroenterology 102:461–467, 1992

    Google Scholar 

  16. Milner P, Crowe R, Kamm MA, Lennard Jones JE, Burnstock G: Vasoactive intestinal polypeptide levels in sigmoid colon in idiopathic constipation and diverticular disease. Gastroenterology 99:666–675, 1990

    Google Scholar 

  17. Pearse AG, Polak JM: Immunocytochemical localization of substance P in mammalian intestine. Histochemistry 41:373–375, 1975

    Google Scholar 

  18. Nilsson J, von Euler AM, Dalsgaard CJ: Stimulation of connective tissue cell growth by substance P and substance K. Nature 315:61–63, 1985

    Google Scholar 

  19. Mantyh PW, Catton MD, Boehmer CG, Welton ML, Passaro EP Jr, Maggio JE, Vigna SR: Receptors for sensory neuropeptides in human inflammatory diseases: Implications for the effector role of sensory neurons. Peptides 10:627–645, 1989

    Google Scholar 

  20. Bartho L, Holzer P: Search for a physiological role of substance P in gastrointestinal motility. Neuroscience 16:1–32, 1985

    Google Scholar 

  21. Ruff MR, Wahl SM, Pert CB: Substance P receptor-mediated chemotaxis of human monocytes. Peptides 6(suppl 2):107–111, 1985

    Google Scholar 

  22. Koizumi M, King N, Lobb R, Benjamin C, Podolsky DK: Expression of vascular adhesion molecules in inflammatory bowel disease. Gastroenterology 103:840–847, 1992

    Google Scholar 

  23. Matis WL, Lavker RM, Murphy GF: Substance P induces the expression of an endothelial-leukocyte adhesion molecule by microvascular endothelium. J Invest Dermatol 94:492–495, 1990

    Google Scholar 

  24. Elitsur Y, Luk GD: Gastrointestinal neuropeptides suppress human colonic lamina propria lymphocyte DNA synthesis. Peptides 11:879–894, 1990

    Google Scholar 

  25. Nagy JI, Hunt SP, Iversen LL, Emson PC: Biochemical and anatomical observations on the degeneration of peptide-containing primary afferent neurons after neonatal capsaicin. Neuroscience 6:1923–1934, 1981

    Google Scholar 

  26. Beuerman RW, Schimmelpfennig B: Sensory denervation of the rabbit cornea affects epithelial properties. Exp Neurol 69:196–201, 1980

    Google Scholar 

  27. Lembeck F, Holzer P: Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn Schmiedebergs Arch Pharmacol 310:175–183, 1979

    Google Scholar 

  28. Levine JD, Collier DH, Basbaum AI, Moskowitz MA, Helms CA: Hypothesis: The nervous system may contribute to the pathophysiology of rheumatoid arthritis. J Rheumatol 12:406–411, 1985

    Google Scholar 

  29. Eedy DJ, Johnston CF, Shaw C, Buchanan KD: Neuropeptides in psoriasis: an immunocytochemical and radioimmunoassay study. J Invest Dermatol 96:434–438, 1991

    Google Scholar 

  30. Naukkarinen A, Nickoloff BJ, Farber EM: Quantification of cutaneous sensory nerves and their substance P content in prosiaris. Journal of Investigative Dermatology 92:126–129, 1989

    Google Scholar 

  31. Byers MR, Swift ML, Wheeler EF: Reactions of sensory nerves to dental restorative procedures. Proc Finn Dent Soc 88(suppl 1):73–82, 1992

    Google Scholar 

  32. de Silva HJ, Millard PR, Kettlewell M, Mortensen NJ, Prince C, Jewell DP: Mucosal characteristics of pelvic ileal pouches. Gut 32:61–65, 1991

    Google Scholar 

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Authors and Affiliations

  1. Second Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland

    Ulla Keränen MD, Tuula Kiviluoto MD, Heikki Järvinen MD, Nils Bäck MD, Eero Kivilaakso MD & Seppo Soinila MD

  2. Department of Anatomy, University of Helsinki, Finland

    Ulla Keränen MD, Tuula Kiviluoto MD, Heikki Järvinen MD, Nils Bäck MD, Eero Kivilaakso MD & Seppo Soinila MD

Authors
  1. Ulla Keränen MD
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  2. Tuula Kiviluoto MD
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  3. Heikki Järvinen MD
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  4. Nils Bäck MD
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  5. Eero Kivilaakso MD
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  6. Seppo Soinila MD
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Additional information

This study has been supported financially by grants from Sigrid Juselius Foundation, Medical Research Council of the Academy of Finland, University of Helsinki, and The Finnish Medical Society Duodecim.

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Keränen, U., Kiviluoto, T., Järvinen, H. et al. Changes in substance P-immunoreactive innervation of human colon associated with ulcerative colitis. Digest Dis Sci 40, 2250–2258 (1995). https://doi.org/10.1007/BF02209015

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  • DOI: https://doi.org/10.1007/BF02209015

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