Interstitial cells of Cajal are present in human extrahepatic bile ducts

Ahmadi, Omid; Nicholson, Martha de L; Gould, Maree; Mitchell, Allan; Stringer, Mark D.

doi:10.1111/j.1440-1746.2009.05980.x

Cited by 45 publications

(30 citation statements)

References 31 publications

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“…ICLCs expressing CD34 but not c-kit have also been observed in human detrusor [Rasmussen et al, 2007] and gut [Pieri et al, 2008] where immunoelectrolabeling confirmed the ultrastructure of CD34+ cells as ICLCs. In several spontaneously active smooth muscle tissues, c-kit-expressing ICLCs appear to be the dominant type [Popescu et al, 2005;Biers et al, 2006;Lang et al, 2007;Lavoie et al, 2007;Ahmadi et al, 2010] including sheep mesenteric lymphatics [McCloskey et al, 2002]. We observed, however, only a subset of lymphatic ICLCs to express c-kit and this is of interest when speculating upon a physiological role for ICLCs in the TD.…”

Section: Interstitial Cajal-like Cellscontrasting

confidence: 48%

“…Interstitial Cajallike cells (ICLCs), or telocytes as they are also known, are morphologically distinct from smooth muscle cells (SMCs) and while they can be identified by expression of proteins specific to them (such as the receptor tyrosine kinase c-kit), ultrastructural assessment by transmission electron microscopy is the unequivocal method for identifying and distinguishing ICLCs from other interstitial cells, such as fibroblasts [Faussone-Pellegrini and Popescu, 2011]. Several spontaneously active smooth musclecontaining tissues expressing c-kit-positive ICLCs have been found in human [Metzger et al, 2004;Metzger et al, 2008;Ahmadi et al, 2010] and animals [Lang et al, 2007;Lavoie et al, 2007], but to date there is only a single report of lymphatic ICLCs from a study of sheep mesenteric lymphatics [McCloskey et al, 2002]. Given that human TD is known to be spontaneously contractile and the suggestion that ICLCs could contribute to this function in other smooth muscles, we proposed that ICLCs could be present in the wall of the human TD.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Interstitial Cajal-Like Cells in the Human Thoracic Duct

Rumessen¹,

Baandrup²,

Mikkelsen³

et al. 2012

Cells Tissues Organs

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Interstitial Cajal-like cells (ICLCs) are speculated to be pacemakers in smooth muscle tissues. While the human thoracic duct (TD) is spontaneously active, the origin of this activity is unknown. We hypothesized that ICLCs could be present in the TD and using histological techniques, immunohistochemistry and immunofluorescence we have investigated the presence of ICLCs, protein markers for ICLCs and the cellular morphology of the human TD. Transmission electron microscopy was employed to investigate ultrastructure. Methylene blue staining, calcium-dependent fluorophores and confocal microscopy were used to identify ICLCs in live tissue. Methylene blue stained cells with morphology suggestive of ICLCs in the TD. Immunoreactivity localized the ICLC protein markers c-kit, CD34 and vimentin to many cells and processes associated with smooth muscle cells (SMCs): coexpression of c-kit with vimentin or CD34 was observed in some cells. Electron microscopy analysis confirmed ICLCs as a major cell type of the human TD. Lymphatic ICLCs possess caveolae, dense bands, a patchy basal lamina, intermediate filaments and specific junctions to SMCs. ICLCs were ultrastructurally differentiable from other interstitial cells observed: fibroblasts, mast cells, macrophages and pericytes. Lymphatic ICLCs were localized to the subendothelial region of the wall as well as in intimate association with smooth muscle bundles throughout the media. ICLCs were morphologically distinct with multiple processes and also spindle shapes. Confocal imaging with calcium-dependent fluorophores corroborated cell morphology and localization observed in fixed tissues. Lymphatic ICLCs thus constitute a significant cell type of the human TD and physically interact with lymphatic SMCs.

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Section: Interstitial Cajal-like Cellscontrasting

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Identification of Interstitial Cajal-Like Cells in the Human Thoracic Duct

Rumessen¹,

Baandrup²,

Mikkelsen³

et al. 2012

Cells Tissues Organs

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“…ICCs are found in the biliary systems of both guinea pigs and humans [23,24]. Gallbladder motility involves various regulatory mechanisms, such as gallbladder smooth Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry muscle and nervous circuit activity, including gallbladder ICCs.…”

Section: Discussionmentioning

confidence: 99%

Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis

Huang¹,

Qiu²,

Yu³

2018

Cell Physiol Biochem

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Background/Aims: Acute cholecystitis is a common gastrointestinal disorder, often characterized by acute cholecystitis with gallbladder motility disorder. Interstitial cells of Cajal (ICCs) are the pacemaker cells of gut motility in the gastrointestinal tract. Disruption of ICC function is related to motility disorders. The aim of this study was to explore the cellular and molecular mechanisms of ICCs in acute cholecystitis and after the resolution of acute inflammation. Materials and Methods: Fifty adult guinea pigs were randomly divided into five groups: a sham-administered group (control group); two groups that were intraperitoneally administered an anti-polyclonal neutrophil (PMN) antibody 24 h before common bile duct ligation (CBDL); and two groups of guinea pigs that were subjected to CBDL without receiving the PMN antibody. Guinea pigs that underwent CBDL were held for 24 h or 48 h after surgery before being subjected to laparotomy and cholecystectomy. Immunohistochemistry, TUNEL assays, western blotting, and real-time PCR were performed to determine ICC morphology and density, to detect ICC apoptosis, and to examine stem cell factor (SCF) and c-kit protein expression and SCF and c-kit mRNA levels, respectively. Results: Both hematoxylin-eosin staining and histological inflammation scores in the PMN groups were lower than those in the control groups (P < 0.01). No differences were observed in ICC morphology between groups. During acute cholecystitis, ICCs numbers were reduced. Conversely, the density of ICCs increased after inflammation was relieved (P < 0.01). In addition, SCF and c-kit protein and mRNA expression levels decreased during acute cholecystitis (P < 0.05) and increased after inflammation was relieved (P < 0.05). Furthermore, ICC apoptosis increased during acute cholecystitis and decreased after resolution of acute cholecystitis (P < 0.01). Conclusions: In acute cholecystitis, ICC injury may be related to gallbladder motility disorder.

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“…In the last century, several studies have found that ICLCs exist in the gut of both human beings and animals, and they have been detected in the esophagus, stomach, small intestine, large bowel, ileum, and colon [16][17][18]. More recently, studies have found that ICLCs are distributed in the gallbladder and extrahepatic biliary duct of both guinea-pigs and humans [18][19][20][21]. Gallbladder motility is regulated by various mechanisms, for instance, the activity of the gallbladder smooth muscle and the nervous circuit, which includes gallbladder ICLCs [15].…”

Section: Discussionmentioning

confidence: 99%

Effect of Neutrophils on Gallbladder Interstitial Cajal-Like Cells in Guinea Pig Model of Acute Cholecystitis

Huang

Qiu

Yang

et al. 2016

Cell Physiol Biochem

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Background: Acute cholecystitis is a common condition in gallbladder motility disorder. Interstitial Cajal-like cells (ICLCs) in the gallbladder are known as one of the players in the complex motility mechanisms affecting gallbladder motility. Aim: This study explored morphological symptoms and molecular mechanisms underlying gallbladder ICLC changes induced by acute cholecystitis. Materials and Methods: Fifteen adult guinea pigs were randomly divided into 3 groups: sham-operated group (healthy controls) and 2 experimental groups wherein these guinea pigs were subjected to common bile duct ligation to induce acute cholecystitis. Neutrophils were isolated from the peripheral blood of sham-operated animals and from the experimental animals at 24 and 48 h after surgery, and co-cultured with gallbladder ICLCs. The morphology of gallbladder ICLCs was examined by laser confocal immunofluorescence microscopy, TUNEL assay was used to detect apoptosis, and western blot and real-time PCR were performed to detect stem cell factor (SCF) and c-kit protein and mRNA expression, respectively. Results: No morphological differences in the gallbladder ICLCs were observed between single-culture and co-culture with healthy control neutrophil groups. However, the ICLCs in all co-culture groups with acute inflammation were impaired. In the co-culture groups, the rate of ICLC apoptosis was significantly higher than that in the single-culture group. SCF and c-kit protein and mRNA expression levels decreased in all co-culture groups as well. Conclusion: We demonstrated that the neutrophils are involved in gallbladder ICLC injury in acute cholecystitis cases and associated with gallbladder motility disorder.

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Interstitial cells of Cajal are present in human extrahepatic bile ducts

Abstract: This study demonstrates for the first time that ICC are present in human extrahepatic bile ducts where they are more densely aggregated than in the gallbladder. This cellular network is likely to be involved in biliary tract motility and its related disorders.

Cited by 45 publications

References 31 publications

Identification of Interstitial Cajal-Like Cells in the Human Thoracic Duct

Identification of Interstitial Cajal-Like Cells in the Human Thoracic Duct

Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis

Effect of Neutrophils on Gallbladder Interstitial Cajal-Like Cells in Guinea Pig Model of Acute Cholecystitis

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