Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differences in dermal mast cell prevalence for adult mice of different strains have been reported previously. In this study, the dermal mast cell prevalence for BALB/c and C57BL/6 mice at 6 weeks of age was similar but as BALB/c mice matured from 6 to 10 weeks of age, their dermal mast cell prevalence halved. In contrast, there was no significant difference in the dermal mast cell prevalence of 6- and 10-week-old C57BL/6 mice. These differences determined the degree of susceptibility of BALB/c and C57BL/6 mice of different ages to UVB (UV radiation of wavelength 280-320 nm)-induced systemic immunosuppression. Expression of the receptor for stem cell factor, Kit protein, was examined on mast cells under conditions in which the dermal mast cell prevalence varied. A significant correlation was observed between Kit expression by mast cells from adult BALB/c, DBA/2 and C57BL/6 mice and dermal mast cell prevalence. In BALB/c mice, mast cell Kit expression decreased as the mice matured from 6 to 10 weeks of age and correlated with the reduction in dermal mast cell numbers. Kit levels on dermal mast cells from C57BL/6 mice were consistently higher than on mast cells from BALB/c mice although significant reductions in Kit were also measured with ageing from 6 to 10 weeks. We hypothesize that regardless of the extent of Kit expression, the dermal mast cell populations were maximally expanded in C57BL/6 mice. We suggest that BALB/c mice of 6 and 10 weeks of age are useful hosts in which to quantitatively evaluate mast cell involvement in a range of functional assays involving skin.
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PMID:Age-related changes in dermal mast cell prevalence in BALB/c mice: functional importance and correlation with dermal mast cell expression of Kit. 1058 93

Elevated mean IL-9 serum levels have been observed in human neonates who will later develop cerebral palsy. In earlier studies, using a newborn mouse model of excitotoxic lesions mimicking those described in human cerebral palsy, we found that IL-9 pretreatment exacerbated brain damage produced by intracerebral injections of the glutamatergic analog ibotenate. Among its different cell targets, the Th2 cytokine IL-9 is a mast cell growth and differentiation factor that can cause mast cells to release various substances including histamine. In the present study, we sought to determine whether the deleterious effects of IL-9 in our mouse model were mediated by mast cells through histamine release. All mouse pups were pretreated with intraperitoneal injections of IL-9 or saline between postnatal days (P) P1 and P5. Immunohistochemistry for murine mast cell protease-1 performed on P5 showed an increased density of labeled cells in the neopallium of IL-9-treated Swiss pups as compared with controls. Western blot analysis confirmed the increased murine mast cell protease-1 brain content of IL-9-treated Swiss mice. IL-9 pretreatment had no significant effect on ibotenate-induced excitotoxic brain lesions in mast cell-deficient P5 pups (WBB6F1/J kit(W/W-v)), whereas IL-9 exacerbated these lesions in the control littermates with normal mast cell populations. Finally, cromoglycate or antihistamine drugs significantly reduced ibotenate-induced brain lesions in IL-9-treated Swiss pups. Taken together, these data suggest that recruitment of cerebral mast cells with histamine release may contribute to the exacerbation of neonatal excitotoxic brain lesions produced by IL-9. Neuroprotective strategies targeting mast cells may be useful in some neonates at risk for cerebral palsy.
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PMID:Deleterious effects of IL-9-activated mast cells and neuroprotection by antihistamine drugs in the developing mouse brain. 1147 7

Genetic loss of surface Fas antigen expression leads to reduced apoptosis of myeloid and lymphoid progenitor cells, and a propensity to develop autoimmunity and myeloid leukemia in mouse models. Oncogenic p21(ras) decreases surface Fas antigen expression and renders fibroblasts resistant to Fas mediated apoptosis. Neurofibromin, which is encoded by NF1, is a GTPase activating protein that negatively regulates p21(ras) activity. NF1 loss leads to deregulation of p21(ras)-effector pathways, which control myeloid cell survival. Heterozygous inactivation of Nf1 increases mast cell numbers in Nf1 +/- mice, and enhances mast cell survival in response to c-kit ligand (kit-L). Here, we show that Nf1-deficient mast cells have reduced surface Fas antigen expression in response to kit-L and are resistant to Fas ligand-mediated apoptosis. Using genetic intercrosses between Nf1 +/- and class I (A)-PI-3K-deficient mice, we demonstrate that hyperactivation of the p21(ras)-class I(A) PI-3K pathway is the mechanism for this phenotype. Finally, we demonstrate that mast cells from both Fas antigen-deficient mice and Nf1 +/- mice are resistant to apoptosis following kit-L withdrawal in vivo. Thus, therapies designed to decrease p21(ras) activity and up-regulate Fas antigen expression may limit the pathological accumulation of myeloid cells in disease states where p21(ras) is hyperactivated.
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PMID:Loss of the nf1 tumor suppressor gene decreases fas antigen expression in myeloid cells. 1503 34

C-kit encodes a transmembrane protein with intrinsic tyrosine kinase activity, which functions as the receptor for stem cell factor. It is expressed on a variety of cell types, including mast cells, hematopoietic progenitor cells, melanocytes, germ cells, and gastrointestinal pacemaker cells. Mutations resulting in alteration of Kit function are associated with diseases involving each of these cells. Recent development of tyrosine kinase inhibitors led to their evaluation as novel therapies for diseases associated with Kit activation. This review will discuss the pathobiology of Kit in human disease, with a particular emphasis on implications for potential targeted treatment strategies in mast cell disease.
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PMID:The biology of Kit in disease and the application of pharmacogenetics. 1524 38

The interstitial cells of Cajal (ICC) play an important role in the control of gut motility. The recognition that the ICC cell membrane harbors the c-kit receptor (CD117) sparked rapid advancement in ICC research on the gut and certain pathologies using immunochemical and molecular methods. The question arises whether ICC exist in the upper urinary tract (UUT) and trigger motility. The present study analyzed the distribution of the c-kit receptor in the normal human UUT compared with various species. Immunohistochemistry (alkaline-phosphatase-anti-alkaline-phosphatase technique, immunofluorescence) was applied on serial sections using monoclonal and polyclonal antibodies recognizing the c-kit receptor. C-kit staining was compared with standard endothelial, epithelial, neurogenic, histiocytic, mast cell, and smooth muscle markers, as well as a negative control. Normal proximal, middle, and distal ureter segments were analyzed in rodents, carnivores, porcines, cow, and humans. In all species the c-kit receptor was detected in either round or spindle-shaped cells. Because of their antigenic profile, the round cells were identified as mast cells occurring in all layers of the ureteral wall except the urothelium and were more frequent in humans. In contrast, the population of spindle-shaped cells was marked only by anti-c-kit receptor antibodies, thus resembling ICC. These ICC-like cells were found among the inner and outer smooth muscle layers and in the lamina propria of all species. In humans, spindle-shaped cells were also found vertically oriented within the urothelium. Our morphological data present for the first time the distribution of ICC in the UUT of various species. The ubiquitous distribution in the entire pyeloureteral complex provides strong evidence that ICC generate electrical pacemaker activity within the UUT as an intrinsic system. Animal studies may help to understand the physiological importance of these ICC-like cells. The significance of these findings needs to be evaluated by functional studies and investigations of certain congenital pathologies with disturbance of the urinary outflow.
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PMID:Cajal-like cells in the upper urinary tract: comparative study in various species. 1565 10

This article reviews the literature on mast cells and tumours derived from mast cells in the dog. Mast cells play a central role in inflammatory and immune reactions. Mast cells, normal and neoplastic, contain and release important biologically active substances: heparin, histamine, eosinophilic chemotactic factor and proteolytic enzymes. Mast cell tumours occur in the dog, particularly in the boxer and related breeds, in the skin and less frequently in the intestines. Cytology usually provides an accurate diagnosis, but histological examination adds further information concerning the histologic grade and the completeness of surgical therapy. Cutaneous mast cell tumours should be regarded as potentially malignant and therefore be removed widely (3 cm. margin). Local recurrence, regional and distant metastases together with paraneoplastic disorders may cause the death of the pet. Histologic grading (2 or 3 grades) and clinical staging together with kinetic parameters and breed (boxers have relatively benign tumours) are important prognostic parameters. Based on prognostic criteria, surgical treatment should be completed with adjuvant radiotherapy, corticosteroids and eventually with combined chemotherapy. A novel, promising therapy is the application of the receptor kinase inhibitor. The study of the pathogenesis of mast cell tumours received new impetus by the finding of mutations, deletions and duplications, in exons 11 and 12 of the C-kit oncogene. Further study of physiological and oncological aspects of mast cells are favoured by the availability of mast cells isolated from spontaneous mast cell tumours and of cultured cell lines.
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PMID:Mast cells and canine mast cell tumours. A review. 1566 12

Mast cell is a hematopoietic lineage dependent on Kit signaling for growth, differentiation, and survival. Mast cells are found in excessive numbers in tissues in a heterogeneous group of disorders collectively known as mastocytosis. Last decade has witnessed important advancements in our understanding of the molecular pathology of mastocytosis. First, systemic mastocytosis has been found to be associated with activating codon 816 mutations of the c-kit gene. Second, this mutation was used as a tracking marker to elucidate the clonal nature of mastocytosis. These findings have resulted in consideration of systemic mastocytosis as a clonal neoplastic disorder of a hematopoietic progenitor cell. Improved knowledge of the mechanisms causing pathological mast cell growth will lead to the discovery of novel treatment options including drugs targeting the mutated Kit protein.
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PMID:Clonality and molecular pathogenesis of mastocytosis. 1599 26

Mast cells are crucial to the development of chronic allergic inflammation and are likely to play a critical role in host defense. In this chapter methodology for histamine and cytokine assays is provided. Crosslinkage of IgE receptor I (Fc epsilonRI) on cord blood-derived mast cells by myeloma IgE and anti-human IgE is used to induce histamine release. Histamine levels were measured in the culture supernatants using an enzyme-linked immunosorbent assay. A human mast cell line (HMC-1), derived from a patient with mast cell leukemia, was activated with interleukin (IL)-1beta to study cytokine production and gene expression. Cytokine gene expression was evaluated by reverse transcriptase polymerase chain reaction and cytokine production was assayed in culture supernatants using an enzyme-linked immunosorbent assay kit.
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PMID:Mast cell histamine and cytokine assays. 1611 Jan 60

Inhalation of crystalline silica results in pulmonary fibrosis and silicosis. It has been suggested that mast cells play a role in these conditions. How mast cells would influence pathology is unknown. We thus explored mast cell interactions with silica in vitro and in B6.Cg-kit(W-sh) mast cell-deficient mice. B6.Cg-kit(W-sh) mice did not develop inflammation or significant collagen deposition after instillation of silica, while C57Bl/6 wild-type mice did have these findings. Given this supporting evidence of a role for mast cells in the development of silicosis, we examined the ability of silica to activate mouse bone marrow-derived mast cells (BMMC), including degranulation (beta-hexosaminidase release); production of reactive oxygen species (ROS) and inflammatory mediators; and the effects of silica on Fc epsilon RI-dependent activation. Silica did not induce mast cell degranulation. However, TNF-alpha, IL-13, monocyte chemotactic protein-1, protease activity, and production of ROS were dose-dependently increased after silica exposure, and production was enhanced after Fc epsilon RI stimulation. This mast cell activation was inhibited by anti-inflammatory compounds. As silica mediates some effects in macrophages through scavenger receptors (SRs), we first determined that mast cells express scavenger receptors; then explored the involvement of SR-A and macrophage receptor with colleagenous structure (MARCO). Silica-induced ROS formation, apoptosis, and TNF-alpha production were reduced in BMMC obtained from SR-A, MARCO, and SR-A/MARCO knockout mice. These findings demonstrate that silica directs mast cell production of inflammatory mediators, in part through SRs, providing insight into critical events in the pathogenesis and potential therapeutic targets in silicosis.
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PMID:Silica-directed mast cell activation is enhanced by scavenger receptors. 1690 92

Interstitial cells of Cajal (ICC) are well described in the bowel wall. They are c-kit positive and play a role as pacemaker cells. Similar c-kit-positive cells have recently been described in the human bladder. The aim of this study was to characterize interstitial cells of the bladder detrusor using a panel of antibodies directed against CD117/c-kit, CD34, CD31, S100, tryptase, neurofilament, NSE, Factor-VIII and GFAP. A striking finding was an interstitial type of cell which is CD34 immunoreactive (CD34-ir) but CD117/c-kit negative. The cells have a tentacular morphology, enveloping and intermingling with individual muscle fasicles. Morphologically and immunohistochemically, they show no neurogenic, endothelial or mast cell differentiation. Transmission electron microscopy (TEM) showed the presence of interstitial cells with a round-to-oval nucleus, sparse perinuclear cytoplasm and long flattened processes, ramifying primarily in a bipolar fashion. Using immunoelectron microscopy (I-TEM) it was possible to view CD34 gold labelling of cells corresponding to interstitial cells. Although similar CD34-positive cells have been demonstrated in the bowel wall, they have never been described in the detrusor. The ontogeny and function of CD34-ir, a kit-negative cell, is unknown, but it may be involved in smooth muscle contraction.
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PMID:CD34-positive interstitial cells of the human detrusor. 1809 58


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