Apoptotic cell death of human interstitial cells of Cajal.
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.
Gibbons
S J
SJ
Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. gibbons.simon@mayo.edu
De Giorgio
R
R
Faussone Pellegrini
M S
MS
Garrity-Park
M M
MM
Miller
S M
SM
Schmalz
P F
PF
Young-Fadok
T M
TM
Larson
D W
DW
Dozois
E J
EJ
Camilleri
M
M
Stanghellini
V
V
Szurszewski
J H
JH
Farrugia
G
G
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D003106:Colon / Q000166:cytology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged
Microsc Res Tech. 1999 Nov 15;47(4):248-66
10602286
Hum Reprod. 2005 Oct;20(10):2866-72
15958395
Gut. 2002 Oct;51(4):496-501
12235070
J Neuropathol Exp Neurol. 1994 Nov;53(6):606-16
7525880
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8567-70
12832617
J Histochem Cytochem. 1996 Sep;44(9):959-68
8773561
Cell Tissue Res. 2006 Aug;325(2):211-7
16596393
Gastroenterology. 2000 Jan;118(1):14-21
10611149
J Physiol. 2001 Oct 15;536(Pt 2):555-68
11600689
J Pediatr Gastroenterol Nutr. 2003 Apr;36(4):492-7
12658043
Am J Gastroenterol. 1997 Feb;92(2):332-4
9040218
Neurogastroenterol Motil. 2007 Jul;19(7):585-95
17593140
J Gastrointest Surg. 2005 Jan;9(1):102-8
15623450
Nat Clin Pract Urol. 2005 Nov;2(11):546-54
16474598
Nature. 1995 Jan 26;373(6512):347-9
7530333
Mod Pathol. 2003 Apr;16(4):389-94
12692204
Cancer Res. 2006 Mar 15;66(6):2946-52
16540642
Nature. 2000 Oct 12;407(6805):770-6
11048727
J Neurosci. 2000 Feb 15;20(4):1393-403
10662830
Nat Med. 1998 Jul;4(7):848-51
9662380
Gastroenterology. 2007 Sep;133(3):897-906
17854596
Acta Anat (Basel). 1990;139(1):31-44
2288187
J Histochem Cytochem. 2002 Apr;50(4):449-54
11897797
Gastroenterology. 1999 Jul;117(1):140-8
10381920
Circ Res. 2003 Feb 7;92(2):139-50
12574141
Oncogene. 2006 Jan 26;25(4):588-98
16205646
Biol Reprod. 2005 Feb;72(2):276-83
15385413
J Physiol. 2003 Oct 1;552(Pt 1):119-33
12897177
Can J Physiol Pharmacol. 1990 Nov;68(11):1437-46
2285888
Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):12008-13
8876253
Circulation. 2002 Jun 25;105(25):3039-45
12082000
J Physiol. 1999 Sep 15;519 Pt 3:867-84
10457097
J Pediatr Surg. 1998 Jan;33(1):130-2
9473118
Histol Histopathol. 1997 Oct;12(4):1169-77
9302576
J Physiol. 1994 Oct 1;480 ( Pt 1):91-7
7853230
Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1111-21
12893628
Gastroenterology. 2001 Aug;121(2):427-34
11487552