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)

The ear, skin, and purified serosal mast cells of WBB6F1/J-(+/+) (WB-(+/+)) and WCB6F1/J-(+/+) (WC-(+/+)) mice contain high steady-state levels of the transcripts that encode mouse mast cell protease (mMCP) 2, mMCP-4, mMCP-5, mMCP-6, and mouse mast cell carboxypeptidase A (mMC-CPA). In contrast, no mast cell protease transcripts are present in abundance in the ear and skin of WBB6F1/J-W/Wv (W/Wv) and WCB6F1/J-Sl/Sld (Sl/Sld) mice which are mast cell-deficient in vivo due to defects in their c-kit and c-kit ligand genes, respectively. We now report that the immature bone marrow-derived mast cells (mBMMC) obtained in vitro with recombinant interleukin 3 (rIL-3) or WEHI-3 cell conditioned medium from WB-(+/+), WC-(+/+), W/Wv, and Sl/Sld mice all contain high steady-state levels of the mMCP-2, mMCP-4, mMCP-5, mMCP-6, and mMC-CPA transcripts. As assessed immunohistochemically, mMCP-2 protein and mMCP-5 protein are also present in the granules of mBMMC from WB-(+/+), WC-(+/+), and W/Wv mice. That Sl/Sld and W/Wv mBMMC contain high steady-state levels of five granule protease transcripts expressed by the mature serosal, ear, and skin mast cells of their normal +/+ littermates suggests that c-kit-mediated signal transduction is not essential for inducing transcription of these protease genes. Because rIL-4 inhibits the rIL-10-induced expression of mMCP-1 and mMCP-2 in BALB/cJ mBMMC, the ability of rIL-4 to influence protease mRNA levels in WC-(+/+) mBMMC and W/Wv mBMMC was investigated. Although rIL-10 induced expression of the mMCP-1 transcript in WC-(+/+) and W/Wv mBMMC, rIL-4 was not able to suppress the steady-state levels of the mMCP-1 transcript or any other protease transcript in these cultured mast cells. Thus, not only do BALB/cJ mBMMC express fewer granule proteases than mBMMC from mast cell-deficient strains and their normal littermates but the subsequent induction of late-expressed proteases in BALB/cJ mBMMC is more tightly regulated by IL-3 and IL-4.
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PMID:Mouse bone marrow-derived mast cells (mBMMC) obtained in vitro from mice that are mast cell-deficient in vivo express the same panel of granule proteases as mBMMC and serosal mast cells from their normal littermates. 800 1

Because in humans mast cells and basophils tend to possess nonsegmented and segmented/multi-lobular nuclei, respectively, nuclear morphology has been a major criterion for assessing the lineage of metachromatic cells of hematopoietic origin. Immature metachromatic cells with mono- and multi-lobular nuclei were both obtained when bone marrow cells from BALB/c mice were cultured for 3 weeks in the presence of interleukin-3. Analogous to the indigenous mature mast cells that reside in the peritoneal cavity and skin, both populations of in vitro-derived cells expressed the surface receptor c-kit, the chymase mouse mast cell protease (mMCP) 5, the tryptase mMCP-6, and the exopeptidase carboxypeptidase A (mMC-CPA). Immunogold electron microscopy confirmed the granule location of mMC-CPA and mMCP-6 in both populations of cells, and cytochemical analysis confirmed the presence of chymotryptic enzymes in the granules. Because mature mast cells possessing multi-lobular nuclei also were occasionally found in the skeletal muscle and jejunum of the BALB/c mouse, the V3 mouse mast cell line was used to investigate the developmental relationship of mast cells that have very different nuclear structures. After the adoptive transfer of V3 mast cells into BALB/c mice, v-abl-immortalized mast cells with mono- and multi-lobular nuclei were detected in the lymph nodes and other tissues of the mastocytosis mice that expressed c-kit, mMCP-5, mMCP-6, and mMC-CPA. These studies indicate that mouse mast cells can exhibit varied nuclear profiles. Moreover, the nuclear morphology of this cell type gives no insight as to its protease phenotype or stage of development.
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PMID:Mouse mast cells that possess segmented/multi-lobular nuclei. 920 74

Tissue mast cell development requires stem cell factor (SCF), whereas helminth-induced intestinal mucosal mast cell hyperplasia also requires T cell-derived factors such as IL-3. We generated progenitor mast cells (PrMC) from mouse bone marrow cells (BMC) in vitro with a triad of SCF, IL-6, and IL-10 that exhibit IL-3-mediated mitogenic and maturation responses. SCF/IL-6/IL-10 transiently elicited a cell subpopulation with the phenotype (c-kit(high)Thy-1(low)) of fetal blood promastocytes at 3 wk of culture that progressed within 1 wk to FcepsilonRI-bearing PrMC, designated PrMCTriad. PrMCTriad lacked mouse mast cell carboxypeptidase A (mMC-CPA) protein, required SCF for IL-3-driven thymidine incorporation, and responded to SCF plus IL-3 with strong mMc-CPA immunoreactivity, clarifying distinct sequential roles for SCF and IL-3 in mast cell development. PrMCTriad, arising from BMC through promastocytes, are metamastocytes that acquire microenvironmentally determined phenotypic features.
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PMID:Generation of a novel stem cell factor-dependent mast cell progenitor. 982 Apr 83

This study shows for the first time the presence of interstitial cells of Cajal (ICC) and their possible role in the initiation of spontaneous excitation in the corporal tissue of the guinea-pig penis. ICC, which were identified by their c-kit immunoreactivity, were abundantly distributed in the corporal smooth muscle meshwork. Spontaneous increases in the intracellular calcium concentration ([Ca(2+)](i); calcium transients) were visualized in preparations loaded with the fluorescent dye fura-2. Ca transients originated from the boundary of muscle bundles and then spread throughout the meshwork (Ca waves). Ca waves were strongly suppressed by either CPA (10 microm), ryanodine (50 microm) or 2-APB (10 microm), and their synchronicity was disrupted by 18beta-GA (30 microm). These results suggest that ICC in the corporal tissue may have a role as pacemakers to drive the bulk of smooth muscles, and that intracellular Ca(2+) stores and gap junctions are critical for the generation of spontaneous excitation.
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PMID:Identification of interstitial cells of Cajal in corporal tissues of the guinea-pig penis. 1475 68

To investigate mechanisms underlying the transmission of spontaneous Ca2+ signals in the bladder, changes in intracellular concentrations of Ca2+ ([Ca2+]i) were visualized in isolated detrusor smooth muscle bundles of the guinea-pig urinary bladder loaded with a fluorescent Ca2+ indicator, fura-PE3 or fluo-4. Spontaneous increases in [Ca2+]i (Ca2+ transients) preferentially originated along the boundary of muscle bundles and then spread to the other boundary (Ca2+ waves). The synchronicity of Ca2+ waves across the bundles was disrupted by 18beta-glycyrrhetinic acid (18beta-GA, 40 microm), carbenoxolone (30 microm) or 2-aminoethoxydiphenylborate (2-APB, 50-100 microm), while CPA (10 microm), ryanodine (100 microm), xestospongin C (3 microm) and U-73122 (10 microm) had no effect. Intracellular recordings using two independent microelectrodes demonstrated that 2-APB (100 microm) blocked electrical coupling between detrusor smooth muscle cells. Nifedipine (10 microm) but not nominal Ca2+-free solution diminished the synchronicity of Ca2+ waves before preventing their generation. Staining for c-kit identified interstitial cells (IC) located along both boundaries of muscle bundles. IC were also scattered amongst smooth muscle cells and were more dominantly distributed in connective tissue between muscle bundles. IC generated nifedipine-resistant spontaneous Ca2+ transients, which occurred independently of those of smooth muscles. In conclusion, the propagation of Ca2+ transients in the bladder appears to be exclusively mediated by the spread of action potentials through gap junctions being facilitated by the regenerative nature of L-type Ca2+ channels, without significant contribution of intracellular Ca2+ stores. IC in the bladder may modulate the transmission of Ca2+ transients originating from smooth muscle cells rather than being the pacemaker of spontaneous activity.
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PMID:Role of interstitial cells and gap junctions in the transmission of spontaneous Ca2+ signals in detrusor smooth muscles of the guinea-pig urinary bladder. 1523 94