Get access

Apoptotic cell death of human interstitial cells of Cajal

Authors

  • S. J. Gibbons,

    1. Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, MN, USA
    2. Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA
    3. Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN, USA
    Search for more papers by this author
  • R. De Giorgio,

    1. Department of Internal Medicine & Gastroenterology, University of Bologna, Bologna, Italy
    Search for more papers by this author
  • M. S. Faussone Pellegrini,

    1. Department of Anatomy, Histology, and Forensic Medicine, University of Florence, Florence, Italy
    Search for more papers by this author
  • M. M. Garrity-park,

    1. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA
    Search for more papers by this author
  • S. M. Miller,

    1. Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, MN, USA
    2. Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA
    3. Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN, USA
    Search for more papers by this author
  • P. F. Schmalz,

    1. Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, MN, USA
    2. Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA
    3. Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN, USA
    Search for more papers by this author
  • T. M. Young-fadok,

    1. Division of Colon and Rectal Surgery, Mayo Clinic, Scottsdale, AZ, USA
    Search for more papers by this author
  • D. W. Larson,

    1. Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA
    Search for more papers by this author
  • E. J. Dozois,

    1. Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA
    Search for more papers by this author
  • M. Camilleri,

    1. Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, MN, USA
    2. Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA
    3. Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN, USA
    Search for more papers by this author
  • V. Stanghellini,

    1. Department of Internal Medicine & Gastroenterology, University of Bologna, Bologna, Italy
    Search for more papers by this author
  • J. H. Szurszewski,

    1. Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, MN, USA
    2. Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA
    3. Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN, USA
    Search for more papers by this author
  • G. Farrugia

    1. Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, MN, USA
    2. Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA
    3. Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN, USA
    Search for more papers by this author

Simon J. Gibbons PhD, Enteric NeuroScience Program, Mayo Clinic, Guggenheim 838, 200 First Street SW, Rochester, MN 55905, USA.
Tel: 507 284 9652; fax: 507 284 0266; e-mail: gibbons.simon@mayo.edu

Abstract

Abstract  Interstitial cells of Cajal (ICC) are specialized mesenchyme-derived cells that regulate contractility and excitability of many smooth muscles with loss of ICC seen in a variety of gut motility disorders. Maintenance of ICC numbers is tightly regulated, with several factors known to regulate proliferation. In contrast, the fate of ICC is not established. The aim of this study was to investigate whether apoptosis plays a role in the regulation of ICC numbers in the normal colon. ICC were identified by immunolabelling for the c-Kit receptor tyrosine kinase and by electron microscopy. Apoptosis was detected in colon tissue by immunolabelling for activated caspase-3, terminal dUTP nucleotide end labelling and by ultrastructural changes in the cells. Apoptotic ICC were identified and counted in double-labelled tissue sections. They were identified in all layers of the colonic muscle. In the muscularis propria 1.5 ± 0.2% of ICC were positive for activated caspase-3 and in the circular muscle layer 2.1 ± 0.9% of ICC were positive for TUNEL. Apoptotic ICC were identified by electron microscopy. Apoptotic cell death is a continuing process in ICC. The level of apoptosis in ICC in healthy colon indicates that these cells must be continually regenerated to maintain intact networks.

Ancillary