Skip to main content
Top
Published in: Virchows Archiv 4/2012

01-10-2012 | Original Article

The significantly reduced number of interstitial cells of Cajal in chagasic megacolon (CM) patients might contribute to the pathophysiology of CM

Authors: Sheila Jorge Adad, Gisele Barbosa e Silva, Alessandro Adad Jammal

Published in: Virchows Archiv | Issue 4/2012

Login to get access

Abstract

In addition to neurons, interstitial cells of Cajal (ICC) play an important role in coordinating intestinal motility with a pacemaker function. This study aimed to quantitatively analyze ICC, neurons, and muscular area, the latter to correct for quantitation errors resulting from dilation in case of a megacolon and from the dispersion of ICC that can be attributed to muscular hypertrophy. We analyzed 30 colon samples: ten chagasic megacolon (CM), ten chagasic colons without megacolon (CXM), and ten nonchagasic control patients (NC). We measured the area of muscularis propria and counted the number of neurons of the myenteric plexus in a histological section of an intestinal ring and the number of ICC at the level of the myenteric plexus and circular muscle layer, the latter in a section immunohistochemically stained for CD117. Muscular hypertrophy occurred only in the CM group. Compared to the NC group, we found in the CM group a statistically significant reduction of 80 % in the number of neurons, 60 % in the number of ICC in the myenteric plexus, and 38 % in the area of circular muscle. In the CXM group, these numbers were highly variable, and their reduction, less pronounced. We conclude that the number of ICC is significantly reduced in CM patients, and that this might contribute to the pathophysiology of CM. However, the development of CM requires severe denervation, whereas CXM generally exhibits less than 50 % denervation, favoring the hypothesis that the reduction in ICC number is, in part, a consequence of denervation.
Literature
1.
3.
go back to reference Köberle F (1968) Chagas’ disease and Chagas’ syndromes: the pathology of American trypanosomiasis. Adv Parasitol 6:63–116PubMedCrossRef Köberle F (1968) Chagas’ disease and Chagas’ syndromes: the pathology of American trypanosomiasis. Adv Parasitol 6:63–116PubMedCrossRef
4.
go back to reference Adad SJ, Andrade DCS, Lopes ER, Chapadeiro E (1991) Contribuição ao estudo da anatomia patológica do megaesôfago chagásico. Rev Inst Med Trop São Paulo 33:445–450CrossRef Adad SJ, Andrade DCS, Lopes ER, Chapadeiro E (1991) Contribuição ao estudo da anatomia patológica do megaesôfago chagásico. Rev Inst Med Trop São Paulo 33:445–450CrossRef
5.
go back to reference Adad SJ, Cançado CG, Etchebehere RM, Teixeira VP, Gomes UA, Chapadeiro E, Lopes ER (2001) Neuron count reevaluation in the myenteric plexus of chagasic megacolon after morphometric neuron analysis. Virchows Arch 438:254–258PubMedCrossRef Adad SJ, Cançado CG, Etchebehere RM, Teixeira VP, Gomes UA, Chapadeiro E, Lopes ER (2001) Neuron count reevaluation in the myenteric plexus of chagasic megacolon after morphometric neuron analysis. Virchows Arch 438:254–258PubMedCrossRef
6.
go back to reference Köberle F (1961) Patologia y anatomia patologica de la enfermedad de Chagas. Bol Ofic Sanit Panamer 51:404–428PubMed Köberle F (1961) Patologia y anatomia patologica de la enfermedad de Chagas. Bol Ofic Sanit Panamer 51:404–428PubMed
7.
go back to reference Thuneberg L (1982) Interstitial cells of Cajal: intestinal pacemaker cells? Adv Anat Embryol Cell Biol 71:1–130PubMedCrossRef Thuneberg L (1982) Interstitial cells of Cajal: intestinal pacemaker cells? Adv Anat Embryol Cell Biol 71:1–130PubMedCrossRef
8.
go back to reference Faussone-Pellegrini MS (1992) Histogenesis, structure and relationships of interstitial cells of Cajal (ICC): from morphology to functional interpretation. Eur J Morphol 30:137–148PubMed Faussone-Pellegrini MS (1992) Histogenesis, structure and relationships of interstitial cells of Cajal (ICC): from morphology to functional interpretation. Eur J Morphol 30:137–148PubMed
9.
go back to reference Sanders KM (1996) A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology 111:492–515PubMedCrossRef Sanders KM (1996) A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology 111:492–515PubMedCrossRef
10.
go back to reference Wedel T, Spiegler J, Soellner S, Roblick UJ, Schiedeck TH, Bruch HP, Krammer HJ (2002) Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon. Gastroenterology 123:1459–1467PubMedCrossRef Wedel T, Spiegler J, Soellner S, Roblick UJ, Schiedeck TH, Bruch HP, Krammer HJ (2002) Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon. Gastroenterology 123:1459–1467PubMedCrossRef
11.
go back to reference Farraway L, Ball AK, Huizinga JD (1995) Intercellular metabolic coupling in canine colon musculature. Am J Physiol 268:C1492–C1502PubMed Farraway L, Ball AK, Huizinga JD (1995) Intercellular metabolic coupling in canine colon musculature. Am J Physiol 268:C1492–C1502PubMed
12.
go back to reference Sanders KM, Ordög T, Koh SD, Torihashi S, Ward SM (1999) Development and plasticity of Interstitial Cells of Cajal. Neurogastroenterol Motil 11:311–338PubMedCrossRef Sanders KM, Ordög T, Koh SD, Torihashi S, Ward SM (1999) Development and plasticity of Interstitial Cells of Cajal. Neurogastroenterol Motil 11:311–338PubMedCrossRef
13.
go back to reference Yamataka A, Kato Y, Tibboel D, Murata Y, Sueyoshi N, Fujimoto T, Nishiye H, Miyano T (1995) A lack of intestinal pacemaker (c-kit) in aganglionic bowel of patients with Hirschsprung’s disease. J Pediatr Surg 30:441–444PubMedCrossRef Yamataka A, Kato Y, Tibboel D, Murata Y, Sueyoshi N, Fujimoto T, Nishiye H, Miyano T (1995) A lack of intestinal pacemaker (c-kit) in aganglionic bowel of patients with Hirschsprung’s disease. J Pediatr Surg 30:441–444PubMedCrossRef
14.
go back to reference Yamataka A, Fujiwara T, Kato Y, Okazaki T, Sunagawa M, Miyano T (1996) Lack of intestinal pacemaker (C-KIT-positive) cells in infantile hypertrophic pyloric stenosis. J Pediatr Surg 31:96–98PubMedCrossRef Yamataka A, Fujiwara T, Kato Y, Okazaki T, Sunagawa M, Miyano T (1996) Lack of intestinal pacemaker (C-KIT-positive) cells in infantile hypertrophic pyloric stenosis. J Pediatr Surg 31:96–98PubMedCrossRef
15.
go back to reference Vanderwiden JM, Liu H, De Laet MH, Vanderhaeghen JJ (1996) Study of the interstitial cells of Cajal in infantile hypertrophic pyloric stenosis. Gastroenterology 111:279–288CrossRef Vanderwiden JM, Liu H, De Laet MH, Vanderhaeghen JJ (1996) Study of the interstitial cells of Cajal in infantile hypertrophic pyloric stenosis. Gastroenterology 111:279–288CrossRef
16.
go back to reference Isozaki K, Hirota S, Miyagawa J, Taniguchi M, Shinomura Y, Matsuzawa Y (1997) Deficiency of c-kit + cells in patients with a myopathic form of chronic idiopathic intestinal pseudo-obstruction. Am J Gastroenterol 92:332–334PubMed Isozaki K, Hirota S, Miyagawa J, Taniguchi M, Shinomura Y, Matsuzawa Y (1997) Deficiency of c-kit + cells in patients with a myopathic form of chronic idiopathic intestinal pseudo-obstruction. Am J Gastroenterol 92:332–334PubMed
17.
go back to reference Hagger R, Finlayson C, Kahu F, Oliveira R, Chimelli L, Kumar D (2000) A deficiency of interstitial cells of Cajal in Chagasic megacolon. J Auton Nerv Syst 80:108–111PubMedCrossRef Hagger R, Finlayson C, Kahu F, Oliveira R, Chimelli L, Kumar D (2000) A deficiency of interstitial cells of Cajal in Chagasic megacolon. J Auton Nerv Syst 80:108–111PubMedCrossRef
18.
go back to reference Geraldino RS, Ferreira AJ, Lima MA, Cabrine M, Ramirez LE (2006) Interstitial cells of Cajal in patients with chagasic megacolon originating from a region of old endemicity. Pathophysiology 13:71–74PubMedCrossRef Geraldino RS, Ferreira AJ, Lima MA, Cabrine M, Ramirez LE (2006) Interstitial cells of Cajal in patients with chagasic megacolon originating from a region of old endemicity. Pathophysiology 13:71–74PubMedCrossRef
19.
go back to reference Iantorno G, Bassotti G, Kogan Z, Lumi CM, Cabanne AM, Fisogni S, Varrica LM, Bilder CR, Munoz JP, Liserre B, Morelli A, Villanacci V (2007) The enteric nervous system in chagasic and idiopathic megacolon. Am J Surg Pathol 31:460–468PubMedCrossRef Iantorno G, Bassotti G, Kogan Z, Lumi CM, Cabanne AM, Fisogni S, Varrica LM, Bilder CR, Munoz JP, Liserre B, Morelli A, Villanacci V (2007) The enteric nervous system in chagasic and idiopathic megacolon. Am J Surg Pathol 31:460–468PubMedCrossRef
20.
go back to reference Gibbons SJ, De Giorgio R, Pellegrini MS, Garrity-Park MM, Miller SM, Schmalz PF, Young-Fadok TM, Larson DW, Dozois EJ, Camilleri M, Stanghellini V, Szurszewski JH, Farrugia G (2009) Apoptotic cell death of human interstitial cells of Cajal. Neurogastroenterol Motil 21:85–93PubMedCrossRef Gibbons SJ, De Giorgio R, Pellegrini MS, Garrity-Park MM, Miller SM, Schmalz PF, Young-Fadok TM, Larson DW, Dozois EJ, Camilleri M, Stanghellini V, Szurszewski JH, Farrugia G (2009) Apoptotic cell death of human interstitial cells of Cajal. Neurogastroenterol Motil 21:85–93PubMedCrossRef
21.
go back to reference Côbo EC, Silveira TP, Micheletti AM, Crema E, Adad SJ (2012) Research on Trypanosoma cruzi and analysis of inflammatory infiltrate in esophagus and colon from chronic chagasic patients with and without mega. J Trop Med 2012:232646. Epub 2011 Oct 30 Côbo EC, Silveira TP, Micheletti AM, Crema E, Adad SJ (2012) Research on Trypanosoma cruzi and analysis of inflammatory infiltrate in esophagus and colon from chronic chagasic patients with and without mega. J Trop Med 2012:232646. Epub 2011 Oct 30
22.
go back to reference Vago AR, Macedo AM, Adad SJ, Reis DA, Corrêa-Oliveira R (1996) PCR detection of Trypanosoma cruzi DNA in oesophageal tissues of patients with chronic digestive Chagas’ disease. Lancet 348:891–892PubMedCrossRef Vago AR, Macedo AM, Adad SJ, Reis DA, Corrêa-Oliveira R (1996) PCR detection of Trypanosoma cruzi DNA in oesophageal tissues of patients with chronic digestive Chagas’ disease. Lancet 348:891–892PubMedCrossRef
23.
go back to reference Vago AR, Andrade LO, Leite AA, Reis DA, Macedo AM, Adad SJ, Tostes S Jr, Moreira MCV, Brasileiro Filho G, Pena DJ (2000) Genetic characterization of Trypanosoma cruzi directly from tissues of patients with chronic Chagas disease. Am J Pathol 156:1805–1809PubMedCrossRef Vago AR, Andrade LO, Leite AA, Reis DA, Macedo AM, Adad SJ, Tostes S Jr, Moreira MCV, Brasileiro Filho G, Pena DJ (2000) Genetic characterization of Trypanosoma cruzi directly from tissues of patients with chronic Chagas disease. Am J Pathol 156:1805–1809PubMedCrossRef
24.
go back to reference Vago AR, Silva DM, Adad SJ, Correa-Oliveira R, D’Avila Reis D (2003) Chronic Chagas disease: presence of parasite DNA in the oesophagus of patients without megaesophagus. Trans Rev Soc Trop Med Hyg 97:308–309CrossRef Vago AR, Silva DM, Adad SJ, Correa-Oliveira R, D’Avila Reis D (2003) Chronic Chagas disease: presence of parasite DNA in the oesophagus of patients without megaesophagus. Trans Rev Soc Trop Med Hyg 97:308–309CrossRef
25.
go back to reference Ribeiro dos Santos R, Marquez JO, Von Gal Furtado CC, Ramos de Oliveira JC, Martins AR, Köberle F (1979) Antibodies against neurons in chronic Chagas’ disease. Tropenmed Parasitol 30:19–23PubMed Ribeiro dos Santos R, Marquez JO, Von Gal Furtado CC, Ramos de Oliveira JC, Martins AR, Köberle F (1979) Antibodies against neurons in chronic Chagas’ disease. Tropenmed Parasitol 30:19–23PubMed
26.
go back to reference Teixeira ML, Rezende Filho J, Figueredo F, Teixeira AR (1980) Chagas disease selective affinity and cytotoxicity of Trypanosoma cruzi-immune lymphocytes to parasympathetic ganglion cells. Mem Inst Oswaldo Cruz 75:33–45PubMedCrossRef Teixeira ML, Rezende Filho J, Figueredo F, Teixeira AR (1980) Chagas disease selective affinity and cytotoxicity of Trypanosoma cruzi-immune lymphocytes to parasympathetic ganglion cells. Mem Inst Oswaldo Cruz 75:33–45PubMedCrossRef
27.
go back to reference Van Voorhis WC, Schlekewy L, Trong HL (1991) Molecular mimicry by Trypanosoma cruzi: the F1-160 epitope that mimics mammalian nerve can be mapped to a 12-amino acid peptide. Proc Natl Acad Sci USA 88:5993–5997PubMedCrossRef Van Voorhis WC, Schlekewy L, Trong HL (1991) Molecular mimicry by Trypanosoma cruzi: the F1-160 epitope that mimics mammalian nerve can be mapped to a 12-amino acid peptide. Proc Natl Acad Sci USA 88:5993–5997PubMedCrossRef
28.
go back to reference Pinheiro SW, Rua AMO, Etchebehere RM, Cançado CG, Chica JEL, Lopes ER, Adad SJ (2003) Morphometric study of the fibrosis and mast cells count in the circular colon musculature of chronic Chagas patients with and without megacolon. Rev Soc Bras Med Trop 36:461–466PubMedCrossRef Pinheiro SW, Rua AMO, Etchebehere RM, Cançado CG, Chica JEL, Lopes ER, Adad SJ (2003) Morphometric study of the fibrosis and mast cells count in the circular colon musculature of chronic Chagas patients with and without megacolon. Rev Soc Bras Med Trop 36:461–466PubMedCrossRef
29.
go back to reference Da Silveira AB, Adad SJ, Correa-Oliveira R, Furness JB, D’Avila Reis D (2007) Morphometric study of eosinophils, mast cells, macrophages and fibrosis in the colon of chronic chagasic patients with and without megacolon. Parasitology 134:789–796PubMedCrossRef Da Silveira AB, Adad SJ, Correa-Oliveira R, Furness JB, D’Avila Reis D (2007) Morphometric study of eosinophils, mast cells, macrophages and fibrosis in the colon of chronic chagasic patients with and without megacolon. Parasitology 134:789–796PubMedCrossRef
30.
go back to reference Lyford GL, He CL, Soffer E, Hull TL, Strong SA, Senagore AJ, Burgart LJ, Young-Fadok T, Szurszewski JH, Farrugia G (2002) Pan-colonic decrease in interstitial cells of Cajal in patients with slow transit constipation. Gut 51:496–501PubMedCrossRef Lyford GL, He CL, Soffer E, Hull TL, Strong SA, Senagore AJ, Burgart LJ, Young-Fadok T, Szurszewski JH, Farrugia G (2002) Pan-colonic decrease in interstitial cells of Cajal in patients with slow transit constipation. Gut 51:496–501PubMedCrossRef
31.
go back to reference Horisawa M, Watanabe Y, Torihashi S (1998) Distribution of c-Kit immunopositive cells in normal human colon and in Hirschsprung’s disease. J Pediatr Surg 33:1209–1214PubMedCrossRef Horisawa M, Watanabe Y, Torihashi S (1998) Distribution of c-Kit immunopositive cells in normal human colon and in Hirschsprung’s disease. J Pediatr Surg 33:1209–1214PubMedCrossRef
32.
go back to reference Hagger R, Gharaie S, Finlayson C, Kumar D (1998) Regional and transmural density of interstitial cells of Cajal in human colon and rectum. Am J Physiol 275:G1309–G1316PubMed Hagger R, Gharaie S, Finlayson C, Kumar D (1998) Regional and transmural density of interstitial cells of Cajal in human colon and rectum. Am J Physiol 275:G1309–G1316PubMed
33.
go back to reference Lee JI, Park H, Kamm MA, Talbot IC (2005) Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit constipation and acquired megacolon. J Gastroenterol Hepatol 20:1292–1298PubMedCrossRef Lee JI, Park H, Kamm MA, Talbot IC (2005) Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit constipation and acquired megacolon. J Gastroenterol Hepatol 20:1292–1298PubMedCrossRef
Metadata
Title
The significantly reduced number of interstitial cells of Cajal in chagasic megacolon (CM) patients might contribute to the pathophysiology of CM
Authors
Sheila Jorge Adad
Gisele Barbosa e Silva
Alessandro Adad Jammal
Publication date
01-10-2012
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 4/2012
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-012-1299-7

Other articles of this Issue 4/2012

Virchows Archiv 4/2012 Go to the issue