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Decreased interstitial cells of Cajal in the sigmoid colon of patients with slow transit constipation

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Abstract

Background and aims

Slow transit constipation (STC) is a colonic motor disorder that is characterized by measurably delayed movement of materials through the colon. Although abnormalities in the neuronal networks of the colon have been demonstrated in patients with STC, the etiology of STC remains unclear. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the intestine and have been implied in the pathogenesis of a number of gastrointestinal motility dysfunctions, including idiopathic STC. This study aimed to determine the normal distribution of ICC within the colon of the Chinese and also to determine if ICC are decreased in Chinese STC patients.

Patients and methods

Twelve patients with STC and eight age-matched normal controls were studied. Specimens of sigmoid colon were obtained immediately after resection. ICC were identified with a monoclonal antibody to c-kit by an indirect immunofluorescence method. Immunostained tissues were examined with a laser scanning confocal microscope and the area occupied by ICC was calculated with an image analysis system.

Results

ICC were located in the external muscle layers including myenteric plexus (MP) and submucosal border (SMB). Two types of Kit-positive ICC were observed: bipolar cells characterized by one or two long processes and multipolar cells characterized by long stellate processes extending in various directions. A higher percentage of ICC was present in the MP regions and circular muscle (CM) layers compared with the SMB and longitudinal muscle (LM) layers. Tissues from STC patients showed a considerable decrease in the number of ICC located in the four regions (ICC-LM, ICC-MP, ICC-CM, ICC-SMB), especially the ICC-SMB, in which ICC almost completely disappeared.

Conclusions

Similar distribution of ICC was observed in the normal sigmoid colon of the Chinese. Decreased area of c-kit+ ICC may play an important role in the pathophysiology of STC. It remains to be determined whether the loss of ICC is primary or secondary to another lesion.

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References

  1. Sanders KM, Ordog T, Koh SD, Torihashi S, Ward SM (1999) Development and plasticity of interstitial cells of Cajal. Neruogastroenterol Motil 11:311–338

    Article  CAS  Google Scholar 

  2. Ward SM, Sanders KM (2001) Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside I. Functional development and plasticity of interstitial cells of Cajal networks. Am J Physiol Gastrointest Liver Physiol 281: G602–G611

    CAS  PubMed  Google Scholar 

  3. Burnstock G, Lavin S (2002) Interstitial cells of Cajal and purinergic signaling. Auton Neurosci: Basic and Clinical 97:68–72

    Google Scholar 

  4. Torihashi S, Nishi K, Tokutomi Y, Nishi T, Ward S, Sanders KM (1999) Blockade of kit signaling induces transdifferentiation of interstitial cells of Cajal to smooth muscle phenotype. Gastroenterology 117:140–148

    CAS  PubMed  Google Scholar 

  5. Nakahara M, Isozaki K, Hirota S, Vanderwinden J, Takakura R, Kinoshita K, Miyagawa JI, Chen H, Miyazaki Y, Kiyohara T, Shinomura Y, Matsuzawa Y (2002) Deficiency of KIT-positive cells in the colon of patients with diabetes mellitus. J Gastroenterol Hepatol 17:666–670

    Article  PubMed  Google Scholar 

  6. Porcher C, Baldo M, Henry M, Orsoni P, Jule Y, Ward SM (2002) Deficiency of interstitial cells of Cajal in the small bowel of Crohn’s disease. Am J Gastroenterol 97:118–125

    Article  Google Scholar 

  7. Yamataka A, Ohshiro K, Kobayashi H, Fujiwara T, Sunagawa M, Miyano T (1997) Intestinal pacemaker c-kit+ cells and snapses in allied Hirschsprung’s disorders. J Pediatr Surg 32:1069–1074

    CAS  PubMed  Google Scholar 

  8. Tong WD, Liu BH, Zhang SB, Zhang LY, Huang XK, Gao F (2003) Outcome of total abdominal colectomy for obstinate slow transit constipation. Formosan J Surg 36:112–119

    Google Scholar 

  9. Sjolund K, Fasth S, Ekman R, Hulten L, Jiborn H, Nordgren S, Sundler F (1997) Neuropeptides in idiopathic chronic constipation (slow transit constipation). Neurogastroenterol Motil 9:143–150

    CAS  PubMed  Google Scholar 

  10. Cortesini C, Cianchi F, Infantino A, Lise M (1995) Nitric oxide synthase and VIP distribution in enteric nervous system in idiopathic chronic constipation. Dig Dis Sci 40:2450–2455

    Google Scholar 

  11. Zhao RH, Baig MK, Mack J, Abramson S, Woodhouse S, Wexner SD (2002) Altered serotonin immunoreactivities in the left colon of patients with colonic inertia. Colorectal Dis 4:56–60

    Article  Google Scholar 

  12. Tomita R, Fujisaki S, Ikeda T, Fukuzawa M (2002) Role of nitric oxide in the colon of patients with slow-transit constipation. Dis Colon Rectum 45:593–600

    PubMed  Google Scholar 

  13. 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 123:1459–1467

    PubMed  Google Scholar 

  14. Lyford GL, He CL, Soffer E, Hull TL, Strong SA, Senagore AJ, Burgart LJ, Yong-Fadok T, Szurszewski JH, Farrugia G (2002) Pan-colonic decrease in interstitial cells of Cajal in patients with slow transit constipation. Gut 51:496–501

    Article  CAS  PubMed  Google Scholar 

  15. He CL, Burgart L, Wang L, Pemberton J, Young-Fadok T, Szurszewski J, Farrugia G (2000) Decreased interstitial cell of Cajal volume in patients with slow transit constipation. Gastroenterology 118:14–21

    Google Scholar 

  16. Porter AJ, Wattchow DA, Hunter A, Costa M (1998) Abnormalities of nerve fibers in the circular muscle of patients with slow transit constipation. Int J Colorectal Dis 13:208–216

    Article  CAS  PubMed  Google Scholar 

  17. Ward SM, Burns AJ, Torihashi S, Sanders KM (1994) Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol (Lond) 480:91–97

    Google Scholar 

  18. Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Miskkelsen HB, Bernstein A. (1995) W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373:347–349

    CAS  PubMed  Google Scholar 

  19. Maeda H, Yamagata A, Nishikawa S, Yoshinaga K, Kobayashi S, Nishi K, Nishikawa S (1992) Requirement of c-kit for development of intestinal pacemaker system. Development 116:369–375

    CAS  PubMed  Google Scholar 

  20. Wu JJ, Rothman TP, Gershon MD (2000) Development of the interstitial cell of Cajal: origin, Kit dependence and neuronal and nonneuronal sources of Kit ligand. J Neurosci Res 59:384–401

    CAS  PubMed  Google Scholar 

  21. Epperson A, Hatton WJ, Callaghan B, Doherty P, Walker RL, Sanders KM, Ward KM, Horowitz B (2000) Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal. Am J Physiol Cell Physiol 279: C529–C539

    CAS  PubMed  Google Scholar 

  22. Daniel EE (2001) Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. III. Interaction of interstitial cells of Cajal with neuromediators: an interim assessment. Am J Physiol Gastrointest Liver Physiol 281: G1329–G1332

    CAS  PubMed  Google Scholar 

  23. Torihashi S, Horisawa M, Watanabe Y (1999) c-kit immunoreactive interstitial cells in the human gastrointestinal tract. J Auton Nerv Syst 75:38–50

    CAS  PubMed  Google Scholar 

  24. Hagger R, Gharaie S, Finlayson C, Kumar D (1998) Distribution of the interstitial cells of Cajal in the human anorectum. J Auton Nerv Syst 73:75–79

    Article  CAS  PubMed  Google Scholar 

  25. 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 92:332–334

    CAS  PubMed  Google Scholar 

  26. Yu CS, Kim HC, Hong HK, Chung DH, Kim HJ, Kang GH, Kim JC (2002) Evaluation of myenteric ganglion cells and interstitial cells of Cajal in patients with chronic idiopathic constipation. Int J Colorectal Dis 17:253–258

    Article  PubMed  Google Scholar 

  27. Smith B (1973) Pathologic changes in the colon produced by anthraquinone purgatives. Dis Colon Rectum 16:455–458

    CAS  PubMed  Google Scholar 

  28. Ponti FD, GiorgioRD (2002) The cathartic colon? Aliment Pharmacol Ther 16:643–644

    Article  PubMed  Google Scholar 

  29. Christensen J, Rick GA (1994) Interstitial cells of Cajal in the rat colon are damaged by mild hypoxia. J Auton Nerv Syst 48:175–180

    Article  CAS  PubMed  Google Scholar 

  30. Lu G, Qian X, Berezin I, Telford GL, Huizinga JD, Sarna SK (1997) Inflammation modulates in vitro colonic myoelectric and contractile activity and interstitial cells of Cajal. Am J Physiol 273: G1233–G1245

    CAS  PubMed  Google Scholar 

  31. Jain D, Moussa K, Tandon M, Culpepper-Morgan J, Proctor DD (2003) Role of interstitial cells of Cajal in motility disorders of the bowel. Am J Gastroenterol 98:618–624

    Article  PubMed  Google Scholar 

  32. He CL, Soffer EE, Ferris CD, Walsh RM, Szurszewski JH, Farrugia G (2001) Loss of interstitial cells of Cajal and inhibitory innervation in insulin-dependent diabetes. Gastroenterology 121:427–434

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (NO. 30300156) and the science committee of Chongqing (NO. 7438).

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Authors and Affiliations

  1. Department of General Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 400042, Chongqing, China

    Wei-Dong Tong, Bao-Hua Liu, Lian-Yang Zhang, Lian-Yang Zhang, Sheng-Ben Zhang, Sheng-Ben Zhang & Ying Lei

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Correspondence to Wei-Dong Tong.

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Tong, WD., Liu, BH., Zhang, LY. et al. Decreased interstitial cells of Cajal in the sigmoid colon of patients with slow transit constipation. Int J Colorectal Dis 19, 467–473 (2004). https://doi.org/10.1007/s00384-003-0577-x

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