Alternative Isoforms of the mi Transcription Factor (MITF) Regulate the Expression of mMCP-6 in the Connective Tissue-Type Mast Cells Cultured with Stem Cell Factor

Mast cell development is a complex process that results in the appearance of phenotypically distinct populations of mast cells in different anatomical sites. Mice homozygous for mutations at the W or S1 locus exhibit several phenotypic abnormalities, including a virtual absence of mast cells in all organs and tissues. Recent work indicates that W encodes the c-kit tyrosine kinase receptor, whereas S1 encodes a c-kit ligand that we have designated stem cell factor (SCF). Recombinant or purified natural forms of the c-kit ligand induce proliferation of certain mast cell populations in vitro, and injection of recombinant SCF permits mast cells to develop in mast cell-deficient WCB6F1-S1/S1d mice. However, the effects of SCF on mast cell proliferation, maturation, and phenotype in normal mice in vivo were not investigated. We now report that local administration of SCF in vivo promotes the development of connective tissue-type mast cells (CTMC) in the skin of mice and that systemic administration of SCF induces the development of both CTMC and mucosal mast cells (MMC) in rats. Rats treated with SCF also develop significantly increased tissue levels of specific rat mast cell proteases (RMCP) characteristic of either CTMC (RMCP I) or MMC (RMCP II). These findings demonstrate that SCF can induce the expansion of both CTMC and MMC populations in vivo and show that SCF can regulate at least one cellular lineage that expresses c-kit, the mast cell, through complex effects on proliferation and maturation.

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Stem cell factor has histamine releasing activity in rat connective tissue-type mast cells

Biochemical and Biophysical Research Communications ◽

10.1016/s0006-291x(05)80300-6 ◽

1992 ◽

Vol 183 (3) ◽

pp. 1076-1083 ◽

Cited By ~ 32

Author(s):

Kazunori Nakajima ◽

Koichi Hirai ◽

Masao Yamaguchi ◽

Toshiaki Takaishi ◽

Ken Ohta ◽

...

Keyword(s):

Stem Cell ◽

Mast Cells ◽

Connective Tissue ◽

Stem Cell Factor ◽

Tissue Type

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Characterization of ‘adult-type’ mast cells derived from human bone marrow CD34+ cells cultured in the presence of stem cell factor and interleukin-6. Interleukin-4 is not required for constitutive expression of CD54, FcεRIα and chymase, and CD13 expressi

Clinical & Experimental Allergy ◽

10.1046/j.1365-2222.2002.01373.x ◽

2002 ◽

Vol 32 (6) ◽

pp. 872-880 ◽

Cited By ~ 34

Author(s):

Y. Shimizu ◽

K. Sakai ◽

T. Miura ◽

T. Narita ◽

H. Tsukagoshi ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mast Cells ◽

Stem Cell Factor ◽

Constitutive Expression ◽

Interleukin 4 ◽

Adult Type ◽

Cd34 Cells ◽

Cells Cultured

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Ultrastructural effects of recombinant human hematopoietic stem cell factor on mast cells and basophils from human CD34+ pluripotent progenitor cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010008585x ◽

1991 ◽

Vol 49 ◽

pp. 310-311

Author(s):

J.P. Goff ◽

A. S. Kirshenbaum ◽

J. P. Albert ◽

S.W. Kessler ◽

K. M. Zsebo ◽

...

Keyword(s):

Stem Cell ◽

Mast Cells ◽

Progenitor Cells ◽

Hematopoietic Stem Cell ◽

Stem Cell Factor ◽

Hematopoietic Stem ◽

Human Cd34 ◽

3T3 Fibroblasts ◽

Proliferation And Differentiation ◽

Cells Cultured

Hematopoietic stem cell factor (SCF) is the product of Sl locus in the mouse and is the ligand for the protooncogene c-kit. The human homologue has recently been cloned and recombinant protein (rhSCF) expressed and purified to homogeneity. rhSCF is synergistic with human cytokines in promoting the proliferation and differentiation of human progenitor cells.Human mast cells and basophils have been shown to originate from human bone marrow-derived CD34+ pluripotent progenitor cells cultured in the presence of rhIL-3, and develop granule scroll patterns only when cocultured with mouse 3T3 fibroblasts. Mast cells, from CD34+ cells cultured over agarose surfaces, in the presence of rhIL-3 had granules that contained only homogeneously dense material. To determine the effect of rhSCF on the appearance of mast cells and basophils in culture, highly purified human CD34+ progenitor cells were grown in the presence of rhIL-3, rhSCF, or rhIL-3 in combination with rhSCF over agarose surfaces.

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Hematologic effects of stem cell factor in vivo and in vitro in rodents

Blood ◽

10.1182/blood.v78.3.645.645 ◽

1991 ◽

Vol 78 (3) ◽

pp. 645-650 ◽

Cited By ~ 40

Author(s):

TR Ulich ◽

J del Castillo ◽

ES Yi ◽

S Yin ◽

I McNiece ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mast Cells ◽

Stem Cell Factor ◽

Bone Marrow Cells ◽

Tissue Type ◽

Mouse Bone Marrow ◽

Erythroid Hyperplasia ◽

The Absolute

Abstract Recombinant rat stem cell factor (rrSCF) administered to rats as a single intravenous injection causes a dose-dependent neutrophilia and lymphocytosis as well as the appearance of immature myeloid cells and occasional blast cells in the circulation. Neutrophilia begins at 2 hours, peaks at 4 to 6 hours, and subsides between 12 and 24 hours. Lymphocytosis occurs at 0.5 hours and has subsided by 2 hours. rrSCF- induced neutrophilia and lymphocytosis are abrogated by boiling, demonstrating that endotoxin-contamination of the rrSCF preparation is not responsible for the observed hematologic effects. The bone marrow at 6 hours after injection of rrSCF shows a left-shifted myeloid and erythroid hyperplasia as evidenced by significant increases in the absolute numbers of morphologically recognizable early myeloid and erythroid precursors. A concurrent decrease in the absolute numbers of mature marrow neutrophils is noted, suggesting that the release of marrow neutrophils contributes to the peripheral neutrophilia. After 2 weeks of daily injections of rrSCF, bone marrow smears demonstrate a remarkable mast cell hyperplasia accompanied by a decrease in total marrow cellularity and by a striking erythroid and lymphoid hypoplasia. rrSCF also causes mast cells to appear in the circulation and causes a systemic increase in embryonic connective tissue-type, but not mucosal- type, mast cells. In vitro long-term culture of lineage-depleted mouse bone marrow cells with rrSCF results in an almost pure outgrowth of mast cells.

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Hematologic effects of stem cell factor in vivo and in vitro in rodents

Blood ◽

10.1182/blood.v78.3.645.bloodjournal783645 ◽

1991 ◽

Vol 78 (3) ◽

pp. 645-650

Author(s):

TR Ulich ◽

J del Castillo ◽

ES Yi ◽

S Yin ◽

I McNiece ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mast Cells ◽

Stem Cell Factor ◽

Bone Marrow Cells ◽

Tissue Type ◽

Mouse Bone Marrow ◽

Erythroid Hyperplasia ◽

The Absolute

Recombinant rat stem cell factor (rrSCF) administered to rats as a single intravenous injection causes a dose-dependent neutrophilia and lymphocytosis as well as the appearance of immature myeloid cells and occasional blast cells in the circulation. Neutrophilia begins at 2 hours, peaks at 4 to 6 hours, and subsides between 12 and 24 hours. Lymphocytosis occurs at 0.5 hours and has subsided by 2 hours. rrSCF- induced neutrophilia and lymphocytosis are abrogated by boiling, demonstrating that endotoxin-contamination of the rrSCF preparation is not responsible for the observed hematologic effects. The bone marrow at 6 hours after injection of rrSCF shows a left-shifted myeloid and erythroid hyperplasia as evidenced by significant increases in the absolute numbers of morphologically recognizable early myeloid and erythroid precursors. A concurrent decrease in the absolute numbers of mature marrow neutrophils is noted, suggesting that the release of marrow neutrophils contributes to the peripheral neutrophilia. After 2 weeks of daily injections of rrSCF, bone marrow smears demonstrate a remarkable mast cell hyperplasia accompanied by a decrease in total marrow cellularity and by a striking erythroid and lymphoid hypoplasia. rrSCF also causes mast cells to appear in the circulation and causes a systemic increase in embryonic connective tissue-type, but not mucosal- type, mast cells. In vitro long-term culture of lineage-depleted mouse bone marrow cells with rrSCF results in an almost pure outgrowth of mast cells.

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