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

We determined the distribution of mast cells in nasal mucosa and studied their proliferation. Inferior turbinate mucosa was sampled in 13 patients with allergic rhinitis (allergic group) and 5 without (non allergic group) and stained immunohistochemically using anti mast cell tryptase antibody, anti-c-kit antibody, anti-PCNA antibody, and anti mast cell chymase antibody. Tissue sections stained with anti tryptase antibody revealed a higher degree of infiltration of tryptase-positive cells, i.e., mast cells, in the allergic group than in non allergic group. In the allergic group, the number of tryptase-positive cells, c-kit-positive cells, and PCNA-positive cells was significantly greater in the epithelium and shallow lamina propria than that in the deep lamina propria. Tryptase-positive, c-kit-positive cells, i.e., c-kit-positive mast cells, and tryptase-positive, PCNA-positive cells, i.e., PCNA-positive mast cells, were also abundunt in the epithelium and shallow lamina propria. The stem cell factor and c-kit receptor are reported to play a primary role in mast cell differentiation and proliferation. PCNA-positive cells represent actively proliferating cells. Based on the above, we concluded that mast cells in the epithelium and shallow lamina propria in the allergic group differentiated and proliferated more actively than those in the deep lamina propria.
 ...
PMID:[Differentiation and proliferation of mast cells in nasal mucosa]. 1143 40

Recent data suggest that mast cells (MCs) and their products are involved in the pathophysiology of thrombosis. In the present study, we analyzed the number, distribution, and phenotype of prostate MCs and periprostatic MCs in patients with unilateral periprostatic vein thrombosis (PVT) by immunohistochemical analysis and electron microscopy. MCs reacted with monoclonal antibodies to tryptase, chymase, and c-kit/CD117 and stained positively for tissue-type plasminogen activator (tPA) and urokinase receptor (uPAR/CD87) but did not express detectable urokinase (uPA) or plasminogen activator inhibitors (PAI-1, PAI-2). We found an increase in the mean +/- SEM number of MCs in PVT compared with control (PVT, 14.36 +/- 1.57 vs control, 5.23 +/- 0.57/mm2). The majority of MCs accumulated in the adventitia of thrombosed veins and showed a decrease in chymase expression. As MCs increase in number in PVT and express a profibrinolytic phenotype, we hypothesize that MC-derived molecules have a role in endogenous fibrinolysis.
 ...
PMID:Characterization of human prostate mast cells and their increase in periprostatic vein thrombosis. 1144 59

Mast cells are multifunctional, tissue-dwelling cells capable of secreting a wide variety of mediators. They develop from bone marrow-derived progenitor cells, primed with stem cell factor (SCF), which mediates its actions by interacting with the SCF receptor or c-kit on the cell surface. Mast cells continue their maturation and differentiation in peripheral tissue, developing into two well described subsets of cells, MCT and MCTC cells, varying in content of tryptase and chymase as well as in immunobiology. Mast cells are activated by numerous stimuli, including antigen (acting via the high affinity IgE receptor, Fc?RI), superoxides, complement proteins, neuropeptides and lipoproteins resulting in activation and degranulation. Following activation, these cells express mediators such as histamine, leukotrienes and prostanoids, as well as proteases, and many cytokines and chemokines, pivotal to the genesis of an inflammatory response. Recent data suggests that mast cells may play an active role in such diverse diseases as atherosclerosis, malignancy, asthma, pulmonary fibrosis and arthritis. Mast cells directly interact with bacteria and appear to play a vital role in host defense against pathogens. Drugs, such as glucocorticoids, cyclosporine and cromolyn have been demonstrated to have inhibitory effects on mast cell degranulation or mediator release.
 ...
PMID:The human mast cell: functions in physiology and disease. 1153 8

Mast cells are differentiated in vitro from bone marrow precursors. In this study the development of bone marrow-derived mast cells was examined from histidine decarboxylase deficient (HDC-/-) and wild-type mice in the presence of IL-3. The number of non-adherent, tryptase- and c-kit-positive mast cells in bone marrow-derived cultures of HDC(-/-) mice was decreased compared to that of wild-type (HDC+/+) animals, but within the tryptase- and c-kit-positive cells there was no difference in the expression intensity of both markers between the two groups. Furthermore, less serine proteases mMCP5, mMCP6 and FcepsilonRIalpha mRNA were detected in bone marrow-derived cell cultures originating from HDC-/- mice. Antigen-provoked degranulation through high-affinity FcepsilonI receptor was also lower in HDC-/- mice. The colony assays in semisolid medium yielded a significantly lower ratio of mixed colonies and higher proportion of macrophage colonies from HDC-/- mice-derived bone marrow compared to the wild-type. In the course of the differentiation of HDC-/- --derived mast cells exogenously added histamine is unable to substitute the endogenously missing histamine. Concordantly, alpha-fluoromethyl-histamine, the specific inhibitor of HDC, revealed only a marginal inhibition on the differentiation of tryptase-positive mast cells from wild-type mice. These findings suggest that the effect of histamine on the IL-3-dependent development of bone marrow-derived mast cell differentiation during the early period is crucial and irreplaceable.
 ...
PMID:Bone marrow-derived mast cell differentiation is strongly reduced in histidine decarboxylase knockout, histamine-free mice. 1193 74

AIDS patients often contain HIV-1-infected mast cells (MCs)/basophils in their peripheral blood, and in vivo-differentiated MCs/basophils have been isolated from the blood of asthma patients that are HIV-1 susceptible ex vivo due to their surface expression of CD4 and varied chemokine receptors. Because IL-16 is a ligand for CD4 and/or an undefined CD4-associated protein, the ability of this multifunctional cytokine to regulate the development of human MCs/basophils from nongranulated progenitors residing in cord or peripheral blood was evaluated. After 3 wk of culture in the presence of c-kit ligand, IL-16 induced the progenitors residing in the blood of normal individuals to increase their expression of chymase and tryptase about 20-fold. As assessed immunohistochemically, >80% of these tryptase(+) and/or chymase(+) cells expressed CD4. The resulting cells responded to IL-16 in an in vitro chemotaxis assay, and this biologic response could be blocked by anti-IL-16 and anti-CD4 Abs as well as by a competitive peptide inhibitor corresponding to a sequence in the C-terminal domain of IL-16. The additional finding that IL-16 induces calcium mobilization in the HMC-1 cell line indicates that IL-16 acts directly on MCs and their committed progenitors. IL-16-treated MCs/basophils also are less susceptible to infection by an M/R5-tropic strain of HIV-1. Thus, IL-16 regulates MCs/basophils at a number of levels, including their vulnerability to retroviral infection.
 ...
PMID:IL-16 regulation of human mast cells/basophils and their susceptibility to HIV-1. 1193 73

A novel subtype of myeloid leukemia exhibiting a partial differentiation of mast cell-lineage cells is described. The disease is characterized by an increase in myeloblasts as well as an increase in immature (blast-like) metachromatic cells (>10% in bone marrow or blood smears). Metachromatic cells express KIT (CD117) and tryptase, but lack basophil-related antigens. In contrast to mast cell leukemia/systemic mastocytosis, metachromatic cells do not express CD2 or CD25, do not form multifocal dense aggregates in the bone marrow, and do not exhibit transforming mutations at codon 816 of c-kit. In the few patients recorded so far, a complex karyotype without recurring anomaly was found. The prognosis appears to be grave, although complete remission in response to chemotherapy has been described.
 ...
PMID:Myelomastocytic leukemia: myeloid neoplasm characterized by partial differentiation of mast cell-lineage cells. 1203 70

Combination of stem cell factor (SCF) and interleukin-6 (IL-6) significantly promoted proliferation of human mast cells from cord blood CD34+ cells. Most of the cells, cultured in the presence of SCF and IL-6 for 10 weeks, expressed c-kit and contained a significant amount of histamine and tryptase and a low amount of chymase. Both tryptase-positive chymase-negative mast cells (MC(T)) and tryptase-positive chymase-positive mast cells (MC(TC)) were found in the same colony derived from a single cord blood CD34+ cell, suggesting that MC(T) and MC(TC) develop from common precursor cells. Single-cell culture of CD34+ cells revealed that committed mast cell progenitors are included in CD34+CD38+HLA-DR- cells. IL-4 significantly enhanced high-affinity immunoglobulin E (IgE) receptor (FcepsilonRI) alpha-chain messenger RNA expression and induced FcepsilonRI on SCF-dependent cord blood-derived human mast cells, resulting in high histamine-releasing activity upon cross-linking of FcepsilonRI. Another factor that up-regulated FcepsilonRI was IgE, and a combination of IL-4 and IgE markedly augmented FcepsilonRI expression on the mast cells. IL-4 and IgE may enhance FcepsilonRI expression by distinct mechanisms; IL-4 promotes FcepsilonRI alpha-chain gene transcription and thus increases alpha-chain protein synthesis in the cells, whereas the binding of IgE may anchor the FcepsilonRI on the cell surface, resulting in suppression of internalization of FcepsilonRI. Mast cells are progeny of hematopoietic stem cells. Recent discovery of a xenotransplantation model revealed that human hematopoietic stem cells can proliferate and differentiate into mature mast cells in the mouse skin 3 months after transplantation of human cord blood CD34+ cells, suggesting that this model may pave the way to clarification of the functions of human mast cells in vivo.
 ...
PMID:Cytokines regulate development of human mast cells from hematopoietic progenitors. 1204 63

The c-kit mutation Asp-816-->Val is detectable not only in neoplastic mast cells (MCs) in patients with systemic mastocytosis (SM) but also in most associated hematologic non-MC lineage disease (AHNMD). In order to prove a monoclonal disease evolution we investigated DNA of pooled microdissected single cells for the presence of the mutation in a patient with SM and concomitant chronic myelomonocytic leukemia (CMML). LightCycler melting curve analysis and direct sequencing of nested polymerase chain reaction (PCR) products revealed the c-kit mutation in tryptase-positive MC and in leukemic CD15-positive cells in bone marrow infiltrates, but not in colonic epithelial cells, thus, suggesting a monoclonal evolution of SM and concurrent CMML on the basis of a somatic mutation in a common hematologic progenitor.
 ...
PMID:Detection of c-kit point mutation Asp-816 --> Val in microdissected pooled single mast cells and leukemic cells in a patient with systemic mastocytosis and concomitant chronic myelomonocytic leukemia. 1236 64

Stem cell factor (SCF) and its receptor c-kit take part in the regulation of developmental processes of mast cells, hematopoietic stem cells, and melanocytes, as well as in the growth control of human malignancies. To explore the possible role of the SCF-c-kit system and of mast cells in pancreatic cancer, the concomitant expression and distribution of the two molecules were examined in 17 normal and 26 cancerous human pancreatic tissues and in 6 cultured pancreatic cancer cell lines. Mast cell distribution was also evaluated in the same tissue samples. In addition, the effects of SCF and of the c-kit tyrosine-kinase inhibitor STI571 on the growth of the cancer cell lines and of the normal pancreatic ductal cell line TAKA-1 were assessed. SCF immunoreactivity was absent in acinar, ductal, and islet cells of the normal pancreas and faint in pancreatic cancer tissues and cell lines. In contrast, c-kit was clearly present in some normal and hyperplastic ducts of the normal pancreas, in the cancer cells of 73% of the tumor samples, and in all the cell lines tested. Mast cells, identified by tryptase and chymase immunostaining on consecutive tissue sections, showed immunoreactivity for SCF and c-kit in both normal and cancerous specimens and their number was significantly increased (p = 0.03) in pancreatic cancer compared with the normal pancreas. SCF showed a dose-dependent growth inhibitory effect on TAKA-1 cells (p < 0.001), whereas pancreatic cancer cells were resistant to the SCF-induced growth inhibition. Nonetheless, the growth of TAKA-1 cells and pancreatic cancer cells was inhibited by the c-kit tyrosine kinase inhibitor STI571. In conclusion, the SCF-c-kit system, possibly with the contribution of mast cells, may have a growth-regulating role in the normal pancreas, which is altered during malignant transformation.
 ...
PMID:The stem cell factor-c-kit system and mast cells in human pancreatic cancer. 1242 8

Mastocytosis comprises a heterogeneous group of hematological disorders which are morphologically defined by proliferation and accumulation of tissue mast cells in one or more organs. Clinical manifestations of mastocytosis range from disseminated maculopapular skin lesions (= urticaria pigmentosa [UP]) that may spontaneously regress to highly aggressive neoplasms like mast cell leukemia or mast cell sarcoma. Recently, it could be shown that systemic mastocytosis (SM) is a clonal disorder often exhibiting mutations of c-kit, a protooncogene encoding the tyrosine kinase receptor for stem cell factor (SCF). Mutations of c-kit are considered to play a key role in the pathogenesis of mastocytosis. Therefore, we investigated the unique case of a 36 year-old male patient with indolent systemic mastocytosis (ISM) evolving from UP (cutaneous mastocytosis) by means of histology, immunophenotyping and molecular biology. At the time of initial diagnosis the bone marrow showed only a mild diffuse increase in mast cells but compact infiltrates were missing. The serum tryptase levels were normal. Five years later, however, the bone marrow histology displayed patchycompact mast cell infiltrates, which now allowed to establish the diagnosis of an ISM. The serum tryptase levels at this time were markedly elevated. At both time points, mast cells were analyzed by immunohistochemistry using anti-tryptase antibody AA1, by flow cytometry using antibodies against CD2 and CD25, and nested polymerase chain reaction (PCR) on laser-microdissected, single pooled mast cells. Immunohistochemistry revealed strong tryptase-positivity of mast cells in both cutaneous and bone marrow infiltrates. Flow cytometry yielded an aberrant expression of CD2 and CD25 on bone marrow mast cells. However, repeated thorough PCR analysis failed to unveil c-kit mutation in atypical mast cells of skin and bone marrow samples of both dates. These findings clearly show that ISM can evolve from UP. Moreover, our study provides further evidence that the c-kit mutation Asp-816-Val is not invariably present in ISM.
 ...
PMID:Evolution of urticaria pigmentosa into indolent systemic mastocytosis: abnormal immunophenotype of mast cells without evidence of c-kit mutation ASP-816-VAL. 1268 51


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>