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)

We describe the effect of soluble c-kit ligand (stem cell factor, SCF) on highly purified CD34-positive hemopoietic progenitors from human umbilical cord blood. Progenitor cells were purified from cord blood mononuclear cells by immune rosetting with lineage specific antibodies and subsequent sorting of the rosette-negative population for CD34(BI3C5)-positive cells. This procedure enriched greater than 100-fold for colony forming cells (CFC). Using optimal concentrations of colony-stimulating factors (CSF) without added SCF approximately 2.5% of cells formed colonies. SCF also had CSF activity on this population, up to 0.5% of cells forming small colonies in response to SCF alone. In contrast, the addition of SCF to optimal concentrations of the other growth factors produced a greater than 10-fold increase in colony number. However, the most notable effect was an approximately 100-fold increase in the number of cells in each colony. Equally striking was the very high proportion (50-80%) of mixed colonies (CFU-MIX). These findings suggest the progenitor cell pool in cord blood is skewed towards very early cells. However, when day 14 colonies formed in response to SCF and other factors were assessed for their re-cloning potential they did not contain significant numbers of CFC, implying that SCF did not support the self-renewal of these CD34 positive cord blood progenitor cells. These findings support a role for SCF as an enhancing factor for hemopoietic progenitor cells but it does not promote self-renewal in these populations.
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PMID:The effect of recombinant stem cell factor (SCF) on purified CD34-positive human umbilical cord blood progenitor cells. 137 77

To provide insights into the pathogenesis of Diamond-Blackfan anemia, we examined the in vitro response of erythroid progenitors to the recently isolated ligand for c-kit (stem cell factor, SCF). For these studies, marrow or blood mononuclear cells from 10 Diamond-Blackfan patients were cultured with erythropoietin (Ep), Ep and interleukin-3, Ep and granulocyte-macrophage colony-stimulating factor, or Ep and lymphocyte conditioned media (LCM). These combinations were tested in the presence or absence of SCF. The mean number of cells per erythroid burst increased 5 to 50-fold in cultures containing SCF. Furthermore, many additional erythroid bursts were seen (mean increment 3.2 x baseline values). Although burst-forming unit-erythroid (BFU-E) from all patients responded, there were differences among individuals in the sensitivity of their BFU-E to SCF. In six patients and all control studies, plateau frequencies of erythroid bursts were achieved with less than or equal to 10 ng/mL SCF, whereas in studies from the other four patients, over 50 ng/mL SCF was required. These data invite speculation that the c-kit receptor/ligand axis is involved in the pathogenesis of Diamond-Blackfan anemia. More importantly and regardless of whether the observed patterns of response reflect the primary defect or an epiphenomenon, our data strongly support a therapeutic trial of SCF in patients with Diamond-Blackfan anemia.
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PMID:Diamond-blackfan anemia: in vitro response of erythroid progenitors to the ligand for c-kit. 171 87

The effect of soluble c-kit ligand (stem cell factor, SCF) on human megakaryocytopoiesis of the cells from umbilical cord blood was evaluated in a methylcellulose culture containing human plasma. SCF alone did not stimulate megakaryocyte colony formation by non-phagocytic mononuclear cells (NPMNC), but did so in combination with interleukin (IL)-3, dose-dependently. This stimulatory effect was exhibited more strongly on large megakaryocyte colonies than on small ones. The effects of SCF + IL-3 on the number and size of megakaryocyte colonies exceeded those of IL-6 + IL-3 or of IL-11 + IL-3. The synergistic interaction of SCF with IL-3 was confirmed by using CD34-positive cells. In particular, addition of SCF to the culture with optimal and suboptimal concentrations of IL-3, significantly increased mixed megakaryocyte colony formation as compared with IL-3 alone. Although SCF in combination with IL-6 or IL-11 induced megakaryocyte colonies from NPMNC, these interactions disappeared entirely in the culture using CD34-positive cells. IL-6 or IL-11 significantly increased the size and DNA content of megakaryocytes in the presence of IL-3, while SCF did not affect, or rather decreased, the DNA content. These findings suggest that SCF promotes more strongly the proliferation of primitive rather than mature megakaryocytic progenitors, but does not affect megakaryocytic maturation.
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PMID:Stem cell factor promotes proliferation of human primitive megakaryocytic progenitors, but not megakaryocytic maturation. 751 2

Recent experimental studies in mice have shown that the proto-oncogene c-kit plays a key role in the development of a component of the pacemaker system that is required for generation of autonomic gut motility. These studies further suggest that interaction of the c-kit receptor and its ligand (stem cell factor, SCF) is critical for the development of the enteric nervous system. The authors investigated the presence of c-kit-positive (c-kit+) cells as well as the expression of SCF in bowel from 12 patients with Hirschsprung's disease (HD), 4 patients with total colonic aganglionosis (TCA), 2 patients with extensive aganglionosis (EA) and 14 controls. Our methods involved the use of immunohistochemistry with antihuman c-kit sera and antihuman SCF sera. A few c-kit+ cells were found in the muscle layers of aganglionic bowels from HD, TCA and EA, in contrast to many c-kit+ cells in ganglionic bowel segments from control, HD, and TCA patients. Expression of SCF was identified in the muscle layers as well as in myenteric plexus of ganglionic bowel, in contrast to its absence in the muscle layers of aganglionic bowel specimens. A lack of c-kit and SCF might be of significance for autonomic gut dysmotility in aganglionic bowel segments of patients with HD and allied disorders such as chronic idiopathic intestinal pseudo-obstruction.
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PMID:A lack of intestinal pacemaker (c-kit) in aganglionic bowel of patients with Hirschsprung's disease. 753 78

Many years ago, alert observers noticed among thousands of laboratory mice a few individuals that, unlike their littermates, exhibited areas of white spotting on their fur. No one could have predicted then that an effort to understand the basis for these abnormalities would ultimately contribute to the characterization of a receptor (c-kit) and a corresponding ligand (stem cell factor, SCF) that are critical not only to the migration and development of melanocytes, but also to hematopoiesis, gametogenesis, mast cell development, and, perhaps, development of the central nervous system. Nor could anyone have foretold then that this receptor and ligand would be shown to regulate the development of multiple distinct cellular lineages not only in mice, but also in humans and other primates, or that c-kit and its ligand would be found to influence the secretory function of cells bearing this receptor, as well as their development. Investigation of the effects of SCF on a single cell type, the mast cell, has produced the most complete picture of the spectrum of biological processes that can be regulated by interactions between c-kit and its ligand. This work shows that SCF critically regulates the migration and survival of mast cell precursors, promotes the proliferation of both immature and mature mast cells, enhances mast cell maturation, directly induces secretion of mast cell mediators, and can regulate the extent of mediator release in mast cells activated by IgE-dependent mechanisms. Indeed, SCF may well prove to be one of the most important of the factors influencing mast cell numbers, phenotype, and function in both health and disease. It now seems virtually certain that further studies of c-kit and SCF will produce important new insights into problems as diverse as the regulation of lineage commitment during normal hematopoiesis or the development and function of the central nervous system. And even though an effect on mast cell development was one of the last phenotypic abnormalities to be recognized in mice with mutations affecting the genes encoding c-kit or SCF, mast cells will continue to represent an important model system for analyzing the biology of c-kit and its ligand.
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PMID:The c-kit receptor, stem cell factor, and mast cells. What each is teaching us about the others. 768 64

Myelodysplastic syndromes (MDS) may be accompanied by systemic mastocytosis. The mechanisms which play a role in the evolution of mastocytosis, however, are not well understood. We report on a case of refractory and anemia with ringed sideroblasts (RARS), and co-existing bone marrow mastocytosis. Compact mast cell (MC) infiltrates were detected in bone marrow sections by immunohistochemistry using an antibody to tryptase. In addition, the MC were found to express c-kit, the tyrosine kinase receptor for MGF (mast cell growth factor = stem cell factor, SCF). Activating point mutations in the kinase domain of c-kit (often found in mastocytosis) were not detectable. However, the mononuclear cells (MNC) of the bone marrow expressed mRNA specific for MITF, a transcription factor that regulates expression of c-kit and differentiation of MC. Surprisingly, the c-kit ligand SCF was found to augment expression of MITF mRNA in bone marrow MNC. Whether this augmentation represents a general response (preventing loss of growth factor receptor expression during cell maturation) common to all types of hemopoietic progenitors, or is confined to (some forms of) mastocytosis, remains unknown.
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PMID:Detection of mi transcription factor (MITF) mRNA in a case of myelodysplastic syndrome and bone marrow mastocytosis. 955 2

The receptor tyrosine c-Kit and its cognate ligand, c-Kit ligand (KL, stem cell factor, SCF), are involved in ovarian follicular development in several animal species. We studied the expression of KL and c-Kit using in situ hybridization and immunohistochemistry in donated human ovarian cortical tissue. The KL transcripts were expressed in granulosa cells of primary follicles, whereas the expression of c-Kit was confined to the oocyte and granulosa cells in primary and secondary follicles. We employed an ovarian organ culture using firstly serum-containing and then serum-free medium to study the effects of KL and an anti-c-Kit antibody, ACK2, on the development and survival of ovarian follicles in vitro. Culture of ovarian cortical slices for 7 days resulted in a 37% increase in the number of primary follicles and a 6% increase in secondary follicles. The proportion of viable follicles decreased in all cultures. The addition of KL (1, 10 and 100 ng/ml) into the culture media did not affect the developmental stages of the follicles or the proportion of atretic follicles. Inclusion of ACK2 (800 ng/ml) in the culture medium significantly increased the proportion of atretic follicles on days 7 (49 vs 28% in control cultures) and 14 (62 vs 38%) of culture. In conclusion, c-Kit and KL are expressed in human ovaries during follicular development. Blocking the c-Kit receptor induces follicular atresia. The KL/c-Kit signaling system is likely to control the survival of human ovarian follicles during early follicular development.
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PMID:Kit ligand and c-Kit are expressed during early human ovarian follicular development and their interaction is required for the survival of follicles in long-term culture. 1659 15