The pathomechanism of inflammatory bowel disease (IBD) has not yet been fully demonstrated. However, it is well known that mast cells are present in the gastrointestinal tract, suggesting that mast cells may take part in it. So, we investigated the number of mast cells in IBD, such as ulcerative colitis (UC) and eosinophilic colitis, and showed that the number of mast cells was increased in the inflammatory lesions. We also presented a case of UC which was treated successfully with an antiallergic drug, tranilast. Furthermore, possible new approaches to treating the disease with immunomodulators including suplatast are introduced. However, our investigations were performed with a limited number of patients with IBD, and additional further studies are required to confirm the findings. 1. Introduction Many reports identified changes in mast cells in inflammatory bowel disease (IBD) including ulcerative colitis (UC). UC is chronic inflammatory bowel disorder which shows evidence of activation of the immune system of the colorectum, with exacerbations and remissions [1–5]. However, contradicting data have also been reported regarding the distribution of mast cells in the intestinal mucosa of patients with UC; namely, the number was increased in some studies [6, 7], unchanged [8], and decreased in others [9]. One reason for the discrepancy in mast cell distribution in colonic lesions may be due to differences in the methods used for tissue preparation, such as tissue fixation, staining techniques, and methods of cell counting as described by Craig et al. [10]. In fact, conventional staining methods are inferior to the sensitive immunohistochemical techniques that use antibodies to specific mast cell proteinase such as tryptase, and some immunohistochemical studies have noted that one of the features of UC among IBDs may be a marked increase of mast cells in the affected mucosa [11, 12]. Eosinophilic colitis (EC), a subtype of eosinophilic gastroenteritis, is a disease characterized by peripheral blood eosinophilia and a prominent eosinophilic infiltration in the intestinal mucosa. Some reports suggested possible involvement of food allergy as the mechanism of the disease [13, 14]. Bischoff [15] reported that eosinophils and mast cells seemed to be mutually related in the allergic reaction in digestive tract mucosa. Although mast cells are thought to be critical effector cells in gastrointestinal allergic reactions [16–18], the role of mast cells in EC still remains unclear. In this paper, we investigated the number of mast cells in UC and EC using
References
[1]
J. K. Ritchie, J. Powell-Tuck, and J. E. Lennard-Jones, “Clinical outcome of the first ten years of ulcerative colitis and proctitis,” The Lancet, vol. 1, no. 8074, pp. 1140–1143, 1978.
[2]
F. C. Edwards and S. C. Truelove, “The course and prognosis of ulcerative colitis,” Gut, vol. 4, pp. 299–315, 1963.
[3]
E. Langholz, P. Munkholm, M. Davidsen, and V. Binder, “Course of ulcerative colitis: analysis of changes in disease activity over years,” Gastroenterology, vol. 107, no. 1, pp. 3–11, 1994.
[4]
N. Hiwatashi, T. Yao, H. Watanabe et al., “Long-term follow-up study of ulcerative colitis in Japan,” Journal of Gastroenterology, vol. 30, supplement 8, pp. 13–16, 1995.
[5]
W. Selby, “The natural history of ulcerative colitis,” Bailliere's Clinical Gastroenterology, vol. 11, no. 1, pp. 53–64, 1997.
[6]
C. C. Fox, A. J. Lazenby, W. C. Moore, J. H. Yardley, T. M. Bayless, and L. M. Lichtenstein, “Enhancement of human intestinal mast cell mediator release in active ulcerative colitis,” Gastroenterology, vol. 99, no. 1, pp. 119–124, 1990.
[7]
T. King, W. Biddle, P. Bhatia, J. Moore, and P. B. Miner, “Colonic mucosal mast cell distribution at line of demarcation of active ulcerative colitis,” Digestive Diseases and Sciences, vol. 37, no. 4, pp. 490–495, 1992.
[8]
S. C. Bischoff, J. Wedemeyer, A. Herrmann et al., “Quantitative assessment of intestinal eosinophils and mast cells in inflammatory bowel disease,” Histopathology, vol. 28, no. 1, pp. 1–13, 1996.
[9]
G. Lloyd, F. H. Green, H. Fox, V. Mani, and L. A. Turnberg, “Mast cells and immunoglobulin E in inflammatory bowel disease,” Gut, vol. 16, no. 11, pp. 861–865, 1975.
[10]
S. S. Craig, G. DeBlois, and L. B. Schwartz, “Mast cells in human keloid, small intestine, and lung by an immunoperoxidase technique using a murine monoclonal antibody against tryptase,” The American Journal of Pathology, vol. 124, no. 3, pp. 427–435, 1986.
[11]
Y. Sasaki, M. Tanaka, and H. Kudo, “Differentiation between ulcerative colitis and Crohn's disease by a quantitative immunohistochemical evaluation of T lymphocytes, neutrophils, histiocytes and mast cells,” Pathology International, vol. 52, no. 4, pp. 277–285, 2002.
[12]
Y. Nishida, K. Murase, H. Isomoto et al., “Different distribution of mast cells and macrophages in colonic mucosa of patients with collagenous colitis and inflammatory bowel disease,” Hepato-Gastroenterology, vol. 49, no. 45, pp. 678–682, 2002.
[13]
A. M. Saavedra-Delgado and D. D. Metcalfe, “Interactions between food antigens and the immune system in the pathogenesis of gastrointestinal diseases,” Annals of Allergy, vol. 55, no. 5, pp. 694–702, 1985.
[14]
I. Narama, K. Ozaki, S. Matsushima, and T. Matsuura, “Eosinophilic gastroenterocolitis in iron lactate-overloaded rats,” Toxicologic Pathology, vol. 27, no. 3, pp. 318–324, 1999.
[15]
S. C. Bischoff, “Mucosal allergy: role of mast cells and eosinophil granulocytes in the gut,” Bailliere's Clinical Gastroenterology, vol. 10, no. 3, pp. 443–459, 1996.
[16]
R. F. Lemanske Jr., F. M. Atkins, and D. D. Metcalfe, “Gastrointestinal mast cells in health and disease. Part II,” The Journal of Pediatrics, vol. 103, no. 3, pp. 343–351, 1983.
[17]
N. Oyaizu, Y. Uemura, H. Izumi, S. Morii, M. Nishi, and K. Hioki, “Eosinophilic gastroenteritis: immunohistochemical evidence for IgE mast cell-mediated allergy,” Acta Pathologica Japonica, vol. 35, no. 3, pp. 759–766, 1985.
[18]
B. K. Wershil, “Role of mast cells and basophils in gastrointestinal inflammation,” Chemical Immunology, vol. 61, no. 1, pp. 187–203, 1995.
[19]
Y. Kashiwase, H. Inamura, J. Morioka, Y. Igarashi, K. Kawai-Kowase, and M. Kurosawa, “Quantitative analysis of mast cells in benign and malignant colonic lesions: immunohistochemical study on formalin-fixed, paraffin-embedded tissues,” Allergologia et Immunopathologia, vol. 36, no. 5, pp. 271–276, 2008.
[20]
H. Inamura, Y. Kashiwase, J. Morioka, K. Suzuki, Y. Igarashi, and M. Kurosawa, “Accumulation of mast cells in the interstitium of eosinophilic colitis,” Allergologia et Immunopathologia, vol. 34, no. 5, pp. 228–230, 2006.
[21]
I. Melamed, S. J. Feanny, P. M. Sherman, and C. M. Roifman, “Benefit of ketotifen in patients with eosinophilic gastroenteritis,” The American Journal of Medicine, vol. 90, no. 3, pp. 310–314, 1991.
[22]
R. Odze, “Diagnostic problems and advances in inflammatory bowel disease,” Modern Pathology, vol. 16, no. 4, pp. 347–358, 2003.
[23]
G. F. A. Benfield, R. Bryan, and J. Crocker, “Lamina propria eosinophils and mast cells in ulcerative colitis: comparison between Asians and Caucasians,” Journal of Clinical Pathology, vol. 43, no. 1, pp. 27–31, 1990.
[24]
M. Kurosawa, “Prophylactic antiasthma drugs in Japan,” Journal of Asthma, vol. 27, no. 5, pp. 299–306, 1990.
[25]
M. Kurosawa, “The prophylactic use of anti-asthma drugs in Japan,” ACI News, vol. 4, no. 5, pp. 135–139, 1992.
[26]
M. Kurosawa, “Anti-allergic drug use in Japan: the rationale and the clinical outcome,” Clinical and Experimental Allergy, vol. 24, no. 4, pp. 299–306, 1994.
[27]
A. Koda, H. Nagai, and S. Watanabe, “Inhibition of hypersensitivity reactions by a new drug, N(3′,4′ dimethoxycinnamoyl) anthranilic acid (N-5′),” Journal of Allergy and Clinical Immunology, vol. 57, no. 5, pp. 396–407, 1976.
[28]
H. Azuma, K. Banno, and T. Yoshimura, “Pharmacological properties of N (3′,4′ dimethoxycinnamoyl) anthranilic acid (N-5′), a new anti atopic agent,” British Journal of Pharmacology, vol. 58, no. 4, pp. 483–488, 1976.
[29]
M. Kurosawa, T. Nemoto, T. Tanaka, R. Fueki, and S. Kobayashi, “A case of ulcerative colitis treated successfully with N-(3′, 4′-dimethoxycinnamoyl) anthranilic acid (N-5′),” Arerugi, vol. 30, no. 1, pp. 8–15, 1981 (Japanese).
[30]
M. Kurosawa, T. Nemoto, T. Tanaka, et al., “A therapeutic trial of anti-allergic drugs in the treatment of ulcerative colitis,” Clinical Immunology, vol. 14, supplement 1, pp. 127–137, 1982 (Japanese).
[31]
S. Okamura, Y. Washida, and M. Kurosawa, “A case of ulcerative colitis treated successfully with anti-allergic drug,” Biomedicine and Therapeutics, vol. 24, no. 10, pp. 1217–1219, 1990 (Japanese).
[32]
M. Raithel, S. Winterkamp, A. Pacurar, P. Ulrich, J. Hochberger, and E. G. Hahn, “Release of mast cell tryptase from human colorectal mucosa in inflammatory bowel disease,” Scandinavian Journal of Gastroenterology, vol. 36, no. 2, pp. 174–179, 2001.
[33]
S. H. He, “Key role of mast cells and their major secretory products in inflammatory bowel disease,” World Journal of Gastroenterology, vol. 10, no. 3, pp. 309–318, 2004.
[34]
I. Lilja, C. Gustafson-Svard, L. Franzen, and R. Sj？dahl, “Tumor necrosis factor-alpha in ileal mast cells in patients with Crohn's disease,” Digestion, vol. 61, no. 1, pp. 68–76, 2000.
[35]
M. Wierzbicki and E. Brezinska-Blaszczyk, “The role of mast cells in the development of inflammatory bowel diseases,” Postepy Hig Med Dosw, vol. 21, no. 11, pp. 642–650, 2008 (Polish).
[36]
S. C. Bischoff, A. Lorentz, S. Schwengberg, G. Weier, R. Raab, and M. P. Manns, “Mast cells are an important cellular source of tumour necrosis factor in human intestinal tissue,” Gut, vol. 44, no. 5, pp. 643–652, 1999.
[37]
J. C. J. Oprins, C. Van der Burg, H. P. Meijer, T. Munnik, and J. A. Groot, “Tumour necrosis factor α potentiates ion secretion induced by histamine in a human intestinal epithelial cell line and in mouse colon: involvement of the phospholipase D pathway,” Gut, vol. 50, no. 3, pp. 314–321, 2002.
[38]
M. Ligumsky, V. Kuperstein, H. Nechushtan, Z. Zhang, and E. Razin, “Analysis of cytokine profile in human colonic mucosal FcεRI-positive cells by single cell PCR: inhibition of IL-3 expression in steroid-treated IBD patients,” FEBS Letters, vol. 413, no. 3, pp. 436–440, 1997.
[39]
T. D. Wardle and L. A. Turnberg, “Potential role for interleukin-1 in the pathophysiology of ulcerative colitis,” Clinical Science, vol. 86, no. 5, pp. 619–626, 1994.
[40]
A. Lorentz, S. Schwengberg, C. Mierke, M. P. Manns, and S. C. Bischoff, “Human intestinal mast cells produce IL-5 in vitro upon IgE receptor cross-linking and in vivo in the course of intestinal inflammatory disease,” European Journal of Immunology, vol. 29, no. 5, pp. 1496–1503, 1999.
[41]
M. E. Himmel, Y. Yao, P. C. Orban, T. S. Steiner, and M. K. Levings, “Reguratory T-celly therapy for inflammatory bowel disease: more questions than answers,” Immunology, vol. 136, no. 2, pp. 115–122, 2012.
[42]
M. Gersemann, J. Wehkamp, and E. F. Stange, “Innate immune dysfunction in inflammatory bowel disease,” Journal of Internal Medicine, vol. 271, no. 5, pp. 421–428, 2012.
[43]
N. A. Hering, M. Fomm, and J. D. Shulzke, “Determinants of chronic barrier function in inflammatory bowel disease and potential therapeutics,” Journal of Physiology, vol. 590, no. 5, pp. 1035–1044, 2012.
[44]
S. van der Marel, A. Majowicz, S. van Deventer, H. Petry, D. W. Hommes, and V. Ferreira, “Gene and cell therapy based treatment strategies for inflammatory bowel disease,” World Journal of Gastrointestinal Pathophysiology, vol. 15, no. 2, pp. 114–122, 2011.
[45]
Z. Liu, B. S. Feng, S. B. Yang, X. Chen, J. Su, and P. C. Yang, “Interleukin (IL)-23 suppresses IL-10 in inflammatory bowel disease,” Journal of Biological Chemistry, vol. 287, no. 5, pp. 3591–3597, 2012.
[46]
L. Bene, A. Falus, N. Baffy, and A. K. Fulop, “Cellular and molecular mechanisms in the two major forms of inflammatory bowel disease,” Pathology and Oncology Research, vol. 17, no. 3, pp. 463–472, 2011.
[47]
L. Pastorelli, R. R. Garg, S. B. Hoang et al., “Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 17, pp. 8017–8022, 2010.
[48]
K. Ohtani, Y. Ohtsuka, T. Ikuse et al., “Increased mucosal expression of GATA-3 and STAT-4 in pediatric ulcerative colitis,” Pediatrics International, vol. 52, no. 4, pp. 584–589, 2010.
[49]
E. N. McNamee, J. D. Wermers, J. C. Masterson, et al., “Novel model of Th2-polarized chronic ileitis : the SAMP1 mouse,” Inflammatory Bowel Diseases, vol. 16, no. 5, pp. 743–752, 2010.
[50]
I. J. Fuss, “Is the Th1/Th2 paradigm of immune regulation applicable to IBD?” Inflammatory Bowel Diseases, vol. 14, supplement 2, pp. S110–S112, 2008.
[51]
F. Sanchez-Mu？oz, A. Dominguez-Lopez, and J. K. Yamamoto-Furusho, “Role of cytokines in inflammatory bowel disease,” World Journal of Gastroenterology, vol. 14, no. 27, pp. 4280–4288, 2008.
[52]
E. Bailon, J. Roman, I. Ramis et al., “The new salicylate derivative UR-1505 modulates the Th2/humoral response in a dextran sodium sulphate model of colitis that resembles ulcerative colitis,” Journal of Pharmacological Sciences, vol. 109, no. 2, pp. 315–318, 2009.
[53]
H. Nakase, S. Mikami, and T. Chiba, “Alteration of CXCR4 expression and Th1/Th2 balance of peripheral CD4-positive T cells can be a biomarker for leukocytapheresis therapy for patients with refractory ulcerative colitis,” Inflammatory Bowel Diseases, vol. 15, no. 7, pp. 963–964, 2009.
[54]
R. Aharoni, O. Brenner, A. Cohen, and R. Arnon, “The therapeutic effect of TV-5010 in a murine model of inflammatory bowel disease: dextran induced colitis,” International Immunopharmacology, vol. 8, no. 11, pp. 1578–1588, 2008.
[55]
C. Daniel, N. A. Sartory, N. Zahn et al., “FTY720 ameliorates oxazolone colitis in mice by directly affecting T helper type 2 functions,” Molecular Immunology, vol. 44, no. 13, pp. 3305–3316, 2007.
[56]
H. Tilg and A. Kaser, “Type 1 interferons and their therapeutic role in Th2 regulated inflammatory disorders,” Expert Opinion on Biological Therapy, vol. 4, no. 4, pp. 469–481, 2004.
[57]
Y. Yanagihara, M. Kiniwa, K. Ikizawa et al., “Suppression of IgE production by IPD-1151T (suplatast tosilate), a new dimethylsulfonium agent: (l) regulation of murine IgE response,” Japanese Journal of Pharmacology, vol. 61, no. 1, pp. 23–30, 1993.
[58]
Y. Yanagihara, M. Kiniwa, K. Ikizawa, T. Shida, N. Matsuura, and A. Koda, “Suppression of IgE production by IPD-1151T (suplatast tosilate), a new dimethylsulfonium agent: (2) Regulation of human IgE response,” Japanese Journal of Pharmacology, vol. 61, no. 1, pp. 31–39, 1993.
[59]
M. Shichijo, Y. Shimizu, K. Hiramatsu et al., “IPD-1151T (suplatast tosilate) inhibits interleukin (IL)-13 release but not IL-4 release from basophils,” Japanese Journal of Pharmacology, vol. 79, no. 4, pp. 501–504, 1999.
[60]
H. Nagai, “Recent research and developmental strategy of anti-asthma drugs,” Pharmacology and Therapeutics, vol. 133, no. 1, pp. 70–78, 2012.
