Intramuscular interstitial cells of Cajal associated with mast cells survive nitrergic nerves in achalasia

Zárate, Natalia; Wang, X. Y.; Tougas, Gervais; Anvari, Mehran; Birch, Daniel W.; Mearin, F; Malagelada, J.-R.; Huizinga, Jan D.

doi:10.1111/j.1365-2982.2006.00788.x

Cited by 61 publications

(87 citation statements)

References 42 publications

(42 reference statements)

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“…The hypothesis is that IL-9, secreted from mast cells, is one of the factors that promote ICC survival in human disease. We observed recently in esophageal tissue from patients with achalasia that there is a linear relationship between the number of surviving ICC and the number of mast cells that accumulate in the musculature [39]; piecemeal degranulation of mast cells making contact with ICC was abundant. Since mast cells can secrete IL-9 and stem cell factor [38] a positive influence of mast cells on ICC survival and/or repair seems possible.…”

Section: Discussionmentioning

confidence: 89%

IL-9 enhances growth of ICC, maintains network structure and strengthens rhythmicity of contraction in culture

Ye¹,

Zhu²,

Khan³

et al. 2006

J Cellular Mol Med

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Interstitial cells of Cajal (ICC) perform critical functions in the control of motility of the gastrointestinal (GI) tract both as pacemaker cells and as mediators of neurotransmission [10,12,26,30]. In addition, a lot of evidence has been obtained to support the notion that ICC pathology is an integral part of many motility disorders of the GI tract [33]. There is evidence that ICC are among the first cells to receive injury from an inflammatory insult [3] and loss of ICC has been associated with loss of GI motor function [25,35,36]. Hence it appears crucial to find mechanisms to support maintenance of the ICC network in intestinal pathophysiology and to elucidate the factors regulating growth, differentiation and maintenance of ICC. IL-9 enhances growth of ICC AbstractInterstitial cells of Cajal (ICC) play a critical role in the control of gastrointestinal motility as pacemaker cells and as regulators of enteric innervation. ICC are one of the first cell types that are injured during an inflammatory process and maintenance of ICC health or promotion of growth and development maybe crucial in recovery after injury. The aim of this study was to evaluate the role of IL-9 in the growth, development and maintenance of ICC in culture. IL-9 in concentrations from 0.02 to 1 μg/ml promoted individual ICC growth and maintenance of the ICC network structure inside tissue explants under culture conditions. The number of ICC grown out of the explants increased significantly at day 4 of culture in the presence of 0.02, 0.5 and 1 μg/ml IL-9. In the presence of 0.5 μg/ml IL-9, explants in culture maintained a higher frequency and stabilized the frequency of spontaneous contractile activity. The ultrastructure of the ICC after 4 days in culture was similar to that in situ. Our data indicate that IL-9 promotes ICC growth in culture and it can be hypothesized that IL-9 is a critical factor in the maintenance of ICC health and ICC repair after injury.

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Section: Discussionmentioning

confidence: 89%

IL-9 enhances growth of ICC, maintains network structure and strengthens rhythmicity of contraction in culture

Ye¹,

Zhu²,

Khan³

et al. 2006

J Cellular Mol Med

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“…ICC are frequently surrounded by MC with established membrane-to-membrane contacts. Furthermore, the release of cytoplasmatic vesicles directed to ICC was observed (Zarate et al 2006). The cytoplasmatic vesicles in MC exhibited characteristic morphological changes defined as piecemeal degranulation that is thought to be associated with vesicle-mediated long-lasting release of the vesicle content (Dvorak et al 1994).…”

Section: Discussionmentioning

confidence: 99%

“…There is clear evidence that MC may also contribute to smooth muscle activity and neural stimulation by releasing a variety of substances (Keith et al 1995, Corvera et al 1999, Hollenberg & Bunnett 1999, Reed et al 2003, Vodenicharov et al 2005. Histamines, prostaglandins and leukotrienes are potential paracrine signals in the communication pathways between MC and intrinsic (Zarate et al 2006). Ultrastructural analysis showed that i.m.…”

Section: Discussionmentioning

confidence: 99%

C-kit receptor in the human vas deferens: distinction of mast cells, interstitial cells and interepithelial cells

Metzger¹,

Rolle²,

Fiegel³

et al. 2008

Reproduction

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The molecular mechanisms underlying the regulation of vas deferens (VD) motility and semen emission are still poorly understood. Interstitial cells of Cajal (ICC), which harbour the c-kit receptor (CD117), provide the basis of coordinated gut motility. We investigated whether c-kit receptor-positive cells also exist in the normal human VD. Enzyme and fluorescence immunohistochemical techniques were applied on serial sections of human proximal, middle, and distal VD segments (nZ49) employing 13 different monoclonal and polyclonal antibodies recognizing the c-kit receptor. The c-kit receptor was detected in either round-or spindle-shaped cells. On account of their antigenic profile, the round-and oval-shaped c-kit receptor-positive cells were identified as mast cells (MC) occurring in all layers of the VD except the epithelium. In contrast, two distinct populations of exclusively c-kit receptor-positive spindle-shaped cells were found within the lamina propria and, rarely, in the inner and outer smooth muscle layers, as well as within the epithelium. Different shaped c-kit receptor-positive MC and IC were present in all layers of the human VD. Our findings demonstrate the presence of different c-kit receptor-positive cells also in the human VD. Their rather ubiquitous distribution within the lamina propria and muscle layers suggests that IC and MC may modulate the neuromuscular transmission and the propagation of electrical signals in multiple systems involved in the draining of fluids. The importance of the c-kit receptor-positive interepithelial cells remains unclear.

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“…Myenteric denervation of the distal oesophagus extending into the stomach is characteristically seen at histological examination (Csendes et al 1992) and is selective for inhibitory nitric oxide (Mearin et al 1993;De Giorgio et al 1999;Zarate et al 2006) and vasoactive inhibitory polypeptide (Aggestrup et al 1983;Sigala et al 1995) releasing motor neurons resulting in unopposed excitatory activity. Familial, infectious, genetic and autoimmune mechanisms have all been postulated to contribute to the development of achalasia (Park et al 2005).…”

Section: Idiopathic Achalasiamentioning

confidence: 99%

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Hubball

Martin

Lang

et al. 2009

Progress in Neurobiology

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Dysfunction of the gastrointestinal neuromuscular apparatus (including interstitial cells ofCajal) is presumed to underlie a heterogeneous group of disorders collectively termed gastrointestinal neuromuscular diseases (GINMDs). Humoral (antibody)-mediated autoimmunity directed against ligand-or voltage-gated ion channels or associated proteins involved in neuromuscular transmission is associated with several acquired neuromuscular diseases of the periphery and is now implicated in an increasing number of less well-characterised diseases. Anti-channel antibodies have been reported in small numbers of patients with GINMD, particularly in those with GI dysfunction secondary to an underlying disease such as neoplasia or infection. However, little is known of humoral autoimmunity in primary GINMDs.This thesis investigated the association between anti-channel antibodies and GINMD, and the human GI tract as a potential target of anti-channel antibodies. The presence of antivoltage-and ligand-gated antibodies was investigated in the serum of patients with primary achalasia, enteric dysmotility and intestinal pseudo-obstruction, and in those with GINMD secondary to Chagas' disease. The functional effect of sera from some of these patients on colonic smooth muscle contractility was also characterised. Finally, the distribution of six voltage-gated potassium channels (VGKCs), which serve essential roles in the peripheral and central nervous systems and are known targets of pathological autoantibodies, were investigated in all layers of the human GI tract.Our findings suggest that currently recognised anti-channel antibodies are not a common pathogenic factor in primary GINMDs. Anti-channel antibodies, in particular anti-VGKC antibodies, were however found in a significant number of individuals with Chagas' disease. Furthermore, circulating factors in patients with chagasic GI disease altered GI smooth muscle contractility in vitro which may have pathological relevance to GI

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Intramuscular interstitial cells of Cajal associated with mast cells survive nitrergic nerves in achalasia

Cited by 61 publications

References 42 publications

IL-9 enhances growth of ICC, maintains network structure and strengthens rhythmicity of contraction in culture

IL-9 enhances growth of ICC, maintains network structure and strengthens rhythmicity of contraction in culture

C-kit receptor in the human vas deferens: distinction of mast cells, interstitial cells and interepithelial cells

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

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