Abstract
Crohn’s disease (CD) is a chronic inflammatory bowel disorder of unknown etiology. An involvement of the intestinal lymphatic system has been suggested. Recently, monoclonal antibodies have become available to distinguish lymphatic vessels from blood vessels. The aim of the study was to examine the distribution of lymphatic vessels in ileal and colic walls of patients affected by CD and compare it with healthy controls and other inflammatory bowel diseases. Twenty-eight cases of CD, 13 cases of other inflammatory bowel diseases, and 10 normal ileal and colic walls were studied. Immunohistochemical staining was performed using the monoclonal antibody D2-40. Quantification of lymphatic vessels was performed by identifying four fields with high density of lymphatics and then counting the number of lymphatic vessels at high resolution. Lymphatic diameter was also evaluated by using an ocular micrometer. Lymphatic vessels showed the highest density in CD specimens. The median number of lymphatics was significantly higher both in ileal and colic samples of CD than the other inflammatory diseases as well as normal controls. Moreover, in patients with CD, diffuse lymphangiectasia was also observed. The present data suggest that lymphangiogenesis and lymphangiectasia probably play a role in the pathogenesis of CD.
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References
Abraham C, Cho JH (2006) Functional consequences of NOD2 (CARD15) mutations. Inflamm Bowel Dis 12:641–650
American Gastroenterological Association (1997) Crohn’s disease: yesterday, today and tomorrow. Gastroenterology 112:1028–1030
Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG (1999) LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol 144:789–801
Breiteneder-Geleff S, Soleiman A, Horvat R, Amann G, Kowalski H, Kerjaschki D (1999) Podoplanin—a specific marker for lymphatic endothelium expressed in angiosarcoma. Verh Ges Pathol 83:270–275
Crohn BB, Ginzburg L, Oppenheimer GD (1932) Regional ileitis: a pathologic and clinical entity. J Am Med Assoc 99:1323–1329
Fogt F, Pascha TL, Zhang PJ, Gausas RE, Rahemtulla A, Zimmerman RL (2004) Proliferation of D2-40-expressing intestinal lymphatic vessels in lamina propria in inflammatory bowel disease. Int J Mol Med 13:211–214
Fukunaga M (2005) Expression of D2-40 in lymphatic endothelium of normal tissues and vascular tumours. Histopathology 46:396–402
Geleff S, Schoppmann SF, Oberhuber G (2003) Increase in podoplanin-expressing intestinal lymphatic vessels in inflammatory bowel disease. Virchows Arch 442:231–237
Heatley RV, Bolton PM, Hughes LE, Owen EW (1980) Mesenteric lymphatic obstruction in Crohn’s disease. Digestion 20:307–313
Hong YK, Shin JW, Detmar M (2004) Development of the lymphatic vascular system: a mystery unravels. Dev Dyn 231:462–473
Kahn HJ, Bailey D, Marks A (2002) Monoclonal antibody, D2-40, a new marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol 15:434–440
Kalima TV, Saloniemi H, Rahko T (1976) Experimental regional enteritis in pigs. Scand J Gastroenterol 11:353–362
Kovi J, Duong HD, Hoang CT (1981) Ultrastructure of intestinal lymphatics in Crohn’s disease. Am J Clin Pathol 76:385–394
Kucharzik T, Maaser C, Lugering A, Kagnoff M, Mayer L, Targan S, Domschke W (2006) Recent understanding of IBD pathogenesis: implications for future therapies. Inflamm Bowel Dis 12:1068–1083
Liang P, Hong JW, Ubukata H, Liu HR, Watanabe Y, Katano M, Motohashi G, Kasuga T, Nakada I, Tabuchi T (2006) Increased density and diameter of lymphatic microvessels correlate with lymph node metastasis in early stage invasive colorectal carcinoma. Virchows Arch 448:570–575
Marks A, Sutherland DR, Bailey D, Iglesias I, Law J, Lei M, Yeger H, Banerjee D, Baumal R (1999) Characterization and distribution of an oncofetal antigen (M2A antigen) expressed on testicular germ cell tumours. Br J Cancer 80:569–578
Mooney EE, Walker J, Hourihane DO’B (1995) Relation of granulomas to lymphatic vessels in Crohn’s disease. J Clin Pathol 48:335–338
Schacht V, Ramirez MI, Hong YK, Hirakawa S, Feng D, Harvey N, Williams M, Dvorak AM, Dvorak HF, Oliver G, Detmar M (2003) T1α-podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO J 22:3546–3556
Tonelli P (2000) New developments in Crohn’s disease: solution of doctrinal mysteries and reinstatement as a surgically treatable disease. The process is not a form of enteritis but lymphedema contaminated by intestinal contents. Chir Ital 52:109–121
Wu TF, MacNaughton WK, von der Weid P-Y (2005) Lymphatic vessel contractile activity and intestinal inflammation. Mem Inst Oswaldo Cruz 100(Suppl 1):107–110
Wu TF, Carati CJ, MacNaughton WK, von der Weid P-Y (2006) Contractile activity of lymphatic vessels is altered in the TNBS model of guinea pig ileitis. Am J Physiol Gastrointest Liver Physiol 291:G566–G574
Zeng Y, Wanf F, Williams ED, Chow CW (2005) Lymphatics in the alimentary tract of children in health and disease: study on mucosal biopsies using the monoclonal antibody D2-40. Pediat Dev Pathol 8:541–549
Acknowledgments
The authors wish to thank Prof. M.P. Foschini and Prof. V. Eusebi for critical reading of the manuscript and valuable discussion. A special thanks to Dr. Jeff Brown for editing the manuscript.
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Pedica, F., Ligorio, C., Tonelli, P. et al. Lymphangiogenesis in Crohn’s disease: an immunohistochemical study using monoclonal antibody D2-40. Virchows Arch 452, 57–63 (2008). https://doi.org/10.1007/s00428-007-0540-2
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DOI: https://doi.org/10.1007/s00428-007-0540-2