Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

c-Kit immunopositive cells are considered to be pacemakers and/or mediators of neurotransmission in the gastrointestinal tract. They also correspond to the interstitial cells of Cajal (ICs) in mice. The normal distribution of c-Kit positive cells and their relation to ICs in the human gastrointestinal tract remain unclear. In this study we examine the distribution of c-Kit positive cells and their ultrastructure in normal human tissue. We then classified them and examined their relationship to ICs. Thirty nine samples of gut from the esophagus to the sigmoid colon from humans (ranging in age from a 16 week old fetus to a 57 year old and without motility disorders), were processed for immunohistochemistry, electronmicroscopy and immuno-electronmicroscopy. c-Kit immunopositive cells were located in the external muscle from the lower esophagus to the sigmoid colon, wherever the external muscle was composed of smooth muscle cells, and they were classified morphologically into two groups. Cells in the first group were mainly spindle-shaped bipolar cells with few branches; these cells ran parallel to nearby smooth muscle. Ultrastructurally, they possessed many intermediate filaments and caveolae. The spindle-shaped cells were present in the esophagus, stomach and small intestine. The second group of cells were located only in the colon, and were multipolar or bipolar cells with numerous branches. Cells in the second group were also rich in caveolae and/or smooth endoplasmic reticulum, but intermediate filaments were not prominent. Although both groups of c-Kit immunopositive cells corresponded to ICs, some ICs in the human gut do not appear to express c-Kit immunoreactivity.
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PMID:c-Kit immunoreactive interstitial cells in the human gastrointestinal tract. 993 68

The murine intestinal nematode Trichuris muris provides an invaluable model of human infection with T. trichiura. Hence, analysis of the immunological responses in the mouse may elucidate the mechanisms of immunity to trichuriasis in man. The work described here investigates the roles of eosinophils, mast cells and antibody-dependent cell-mediated cytotoxicity (ADCC) in the elimination of T. muris from the host gut. Following ablation of IL-5, and hence eosinophilia, mice usually resistant to T. muris infection remained so. Further, blocking the stem cell factor receptor, c-kit, to facilitate complete ablation of mast cells over the period of parasite expulsion in resistant mice had no effect on the development of protective immunity. Therefore it can be deduced that eosinophils and mast cells are not critical in resistance. In addition to these studies, the role of antibody-mediated cellular cytotoxic mechanisms was investigated via the analysis of an infection time course in Fc gamma R-/- mice. These animals, on a resistant background, were fully immune and expelled the parasites before development of the adult stage. Thus this model provides evidence against a major role for ADCC in resistance to infection with T. muris. The studies described here have eliminated some of the major effector mechanisms traditionally associated with helminth infection, and work continues to elucidate the critical immune responses associated with resistance.
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PMID:Mast cells, eosinophils and antibody-mediated cellular cytotoxicity are not critical in resistance to Trichuris muris. 1008 71

Intestinal subepithelial myofibroblasts (ISEMF) and the interstitial cells of Cajal are the two types of myofibroblasts identified in the intestine. Intestinal myofibroblasts are activated and proliferate in response to various growth factors, particularly the platelet-derived growth factor (PDGF) family, which includes PDGF-BB and stem cell factor (SCF), through expression of PDGF receptors and the SCF receptor c-kit. ISEMF have been shown to play important roles in the organogenesis of the intestine, and growth factors and cytokines secreted by these cells promote epithelial restitution and proliferation, i.e., wound repair. Their role in the fibrosis of Crohn's disease and collagenous colitis is being investigated. Through cyclooxygenase (COX)-1 and COX-2 activation, ISEMF augment intestinal ion secretion in response to certain secretagogues. By forming a subepithelial barrier to Na(+) diffusion, they create a hypertonic compartment that may account for the ability of the gut to transport fluid against an adverse osmotic gradient. Through the paracrine secretion of prostaglandins and growth factors (e.g., transforming growth factor-beta), ISEMF may play a role in colonic tumorigenesis and metastasis. COX-2 in polyp ISEMF may be a target for nonsteroidal anti-inflammatory drugs (NSAIDs), which would account for the regression of the neoplasms in familial adenomatous polyposis and the preventive effect of NSAIDs in the development of sporadic colon neoplasms. More investigation is needed to clarify the functions of these pleiotropic cells.
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PMID:Myofibroblasts. II. Intestinal subepithelial myofibroblasts. 1044 94

The term 'Interstitial cells of Cajal' (ICC) designates several groups of mesenchymal cells present along the gastro-intestinal tract (GI), in close association with smooth muscle cells and elements of the enteric nervous system (ENS). For years, transmission electron microscopy (TEM) has been the only reliable tool to study ICC. Whilst TEM remains the golden standard for identification of ICC, the observation that the tyrosine kinase receptor c-kit plays a crucial role in their development recently resulted in numerous immunohistochemical studies and also led to a better characterization of their roles. ICC form extensive networks of electrically coupled cells and certain groups of ICC are currently regarded as the source of the spontaneous slow waves of the gut musculature (pacemaker cells). Other ICC appear to be involved in the transduction of the relaxation of smooth muscle triggered by nitric oxide. Abnormal distribution of ICC has been reported in several human diseases and abnormal functioning of ICC might actually be involved in many disorders of GI transit. This review addresses (1) the morphology and relationships of ICC along the GI tract in man and mouse, mainly based on data from immunohistochemistry and confocal microscopy, (2) the emerging role of ICC in the pathophysiology of human diseases, like infantile hypertrophic pyloric stenosis (a common disorder with a dysfunction of the pyloric sphincter), Hirschsprung's disease (aganglion-osis coli) and intestinal pseudo-obstruction, (3) developmental issues, (4) recent reports suggesting a possible link between ICC and gastrointestinal stromal tumors.
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PMID:Role of Interstitial Cells of Cajal and their relationship with the enteric nervous system. 1047 70

Interstitial cells of Cajal (ICC) are the pacemakers in gastrointestinal (GI) muscles, and these cells also mediate or transduce inputs from the enteric nervous system. Different classes of ICC are involved in pacemaking and neurotransmission. ICC express specific ionic conductances that make them unique in their ability to generate and propagate slow waves in GI muscles or transduce neural inputs. Much of what we know about the function of ICC comes from developmental studies that were made possible by the discoveries that ICC express c-kit and proper development of ICC depends upon signalling via the Kit receptor pathway. Manipulating Kit signalling with reagents to block the receptor or downstream signalling pathways or by using mutant mice in which Kit or its ligand, stem cell factor, are defective has allowed novel studies into the specific functions of the different classes of ICC in several regions of the GI tract. Kit is also a surface antigen that can be used to conveniently label ICC in GI muscles. Immunohistochemical studies using Kit antibodies have expanded our knowledge about the ICC phenotype, the structure of ICC networks, the interactions of ICC with other cells in the gut wall, and the loss of ICC in some clinical disorders. Preparations made devoid of ICC have also allowed analysis of the consequences of losing specific classes of ICC on GI motility. This review describes recent advances in our knowledge about the development and plasticity of ICC and how developmental studies have contributed to our understanding of the functions of ICC. We have reviewed the clinical literature and discussed how loss or defects in ICC affect GI motor function.
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PMID:Development and plasticity of interstitial cells of Cajal. 1052 Jan 64

Different populations of interstitial cells (ICs) may serve as gut pacemakers or as intermediaries between enteric nerves and smooth muscle cells. However, very little is known about the substances that ICs might use to communicate with other cells and no data are available in humans. Because carbon monoxide (CO) is emerging as a putative mediator in the regulation of gastrointestinal motility, this study examined the presence of heme oxygenase (HO2), the constitutive form of the enzyme for CO production, in human stomach with particular attention to ICs. The distribution of HO2 in nerves and ICs in human antrum was studied using specific antibodies. The immunostaining was observed using confocal laser scanning microscopy. HO2 immunoreactivity was found in myenteric neurons and nerve fibers supplying the circular muscle layer and in intramuscular c-kit(+) ICs, but not in c-kit(+) ICs surrounding the myenteric ganglia. The presence of HO2 in different cell types suggests that CO may serve as an intercellular messenger between myenteric neurons and ICs and between ICs and smooth muscle cells in human stomach.
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PMID:Distribution of heme oxygenase 2 in nerves and c-kit(+) interstitial cells in human stomach. 1055 Jun 17

Recent studies on the interstitial cells of Cajal (ICC) have determined ultrastructural criteria for the identification of these previously enigmatic cells. This review deals with the electron microscopic findings obtained by the author's research group in different tissue regions of the gut in mice, rats and guinea-pigs, comparing these with reports from other groups in different species and in humans. ICC are characterized by the following morphological criteria: numerous mitochondria, abundant intermediate filaments and large gap junctions which connect the cells with each other and with smooth muscle cells. Due to their location in the gut and the specific species, the ICC are markedly heterogeneous in appearance, ranging from cells closely resembling smooth muscle cells to those similar to fibroblasts (Table 1). Nevertheless, the above-mentioned morphological features are shared by all types of ICC and serve in identifying them. Recent discoveries on a significant role of c- kit in the maturation of the ICC and their specific immunoreactivity to anti-c-Kit antibody have confirmed the view that the ICC comprise an independent and specific entity of cells. This view is reinforced by the findings of the author's group that the ICC characteristically possess vimentin filaments and are stained with the zinc iodide-osmium tetroxide method which provides a staining affinity similar to methylene blue, the dye used in the original work by Cajal, (1911). Developmental studies indicate that the ICC are derived from a non-neuronal, mesenchymal origin. This paper further reviews advances in the physiological studies on the ICC, in support of the hypothesis by THUNEBERG (1982) that they function as a pacemaker in the digestive tract and a mediator transmitting impulses from the nerve terminals to the smooth muscle cells.
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PMID:Ultrastructural characterization of the interstitial cells of Cajal. 1059 41

Disordered gut motor activity is a feature of patients with Chagas' disease: colonic involvement leads to the development of megacolon and symptoms of constipation. Interstitial cells of Cajal are thought to modulate gut motility. The aim of this study was to test the hypothesis that there is an abnormality of the density of distribution of interstitial cells of Cajal in Chagasic megacolon. Interstitial cells of Cajal were identified by immunohistochemistry using an anti-c-kit antibody. Six patients with Chagasic megacolon were compared with normal controls. The density of distribution of interstitial cells of Cajal was assessed in the longitudinal and circular muscle layers, and in the intermuscular plane of the Chagasic and normal colon. Statistical analysis was performed using Fisher's exact test. The interstitial cells of Cajal density in Chagasic megacolon was much reduced in comparison to normal colonic tissue in the longitudinal muscle layer (P=0.0084), intermuscular plane (P<0.0001), and circular muscle layer (P=0.0051). The lack of interstitial cells of Cajal may play a role in the pathophysiology of the disease, leading to the development of megacolon and symptoms of constipation.
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PMID:A deficiency of interstitial cells of Cajal in Chagasic megacolon. 1074 48

Most gastrointestinal stromal tumors (GISTs), a subgroup of mesenchymal neoplasms of the gut wall, express both Kit (CD117) and CD34 proteins. It has been suggested that GISTs originate from or differentiate into interstitial cells of Cajal (ICC), after several reports indicated that ICC are likely the only cells in the gut which express both Kit and CD34. ICC are among the few cell types resident in the gut which express Kit, together with mast cells. However, the question whether or not ICC express CD34 is currently disputed. Using single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) on cultured murine intestinal cells, single ICC were selected by morphology and tested for the expression of c-kit and CD34 mRNA. Most ICC were only c-kit-positive, however a subset (7 out of 43) were double positive for both c-kit and CD34. In the human small intestine, sequential immunohistochemical staining for Kit and CD34 proteins on the same 3-microm sections showed that some of the ICC surrounding Auerbach's plexus and ICC within the circular muscle layer of the small intestine were positive for both Kit and CD34. In addition, CD34(+)Kit(-) cells were seen adjacent to ICC. These data from two different techniques indicate that ICC can be double positive for Kit and CD34. Thus, GISTs with the Kit(+)CD34(+) phenotype may arise from a subpopulation of CD34(+) Kit(+) ICC.
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PMID:Gastrointestinal stromal tumors may originate from a subset of CD34-positive interstitial cells of Cajal. 1075 39

Athymic cytokine receptor gamma chain mutant mice that lack the thymus, Peyer's patches, cryptopatches (CP), and intestinal T cells were reconstituted with wild-type bone marrow cells. Bone marrow-derived TCR(-) intraepithelial lymphocytes (IEL) first appeared within villous epithelia of small intestine overlying the regenerated CP, and these TCR(-) IEL subsequently emerged throughout the epithelia. Thereafter, TCR(+) IEL increased to a comparable number to that in athymic mice and consisted of TCRgammadelta and TCRalphabeta IEL. In gut-associated lymphoid tissues of wild-type mice, only CP harbored a large population of c-kit(high)IL-7R(+)CD44(+)Thy-1(+/-)CD4(+/-)CD25(low/-)alpha(E) beta(7)(-)Lin(-) (Lin, lineage markers) lymphocytes that included cells expressing germline but not rearranged TCRgamma and TCRbeta gene transcripts. These findings provide direct evidence that gut CP develop progenitor T cells for extrathymic IEL descendants.
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PMID:Gut cryptopatches: direct evidence of extrathymic anatomical sites for intestinal T lymphopoiesis. 1111 81


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